iBiology Podcast: Recent Episodes
iBiology
The fat layer in our skin has the ability to expand and shrink. Yet, the regulatory mechanisms for skin fat growth and shrinking are not well understood. In this Share Your Research Talk, Edriss Yousuf describes his thesis research on the regulation of skin fat. He discovered a non-immune function of regulatory T cells and showed that they can induce autophagy in skin fat cells to decrease their lipid droplet size. These findings have implications for scarring and scleroderma, disorders which are typically associated with reduced skin fat abundance.
Dirt is anything but dumb. Inside soil lives a community of microbes that play an important role in everything from the environment to agriculture. In this Share Your Research talk, Dr. Julia Nepper describes her postdoctoral research to model and understand the microbial community inside the rhizosphere, the soil adjacent to plant roots. Dr. Nepper performed a series of experiments to understand how three key microbial species interact with one another to support each other’s growth and survival. These findings indicate that the soil microbiome is greater than the sum of its parts, and underscores the importance of modeling complex species
In this session, you will learn how to thoughtfully choose your next job opportunity and successfully negotiate with both your current research advisor and prospective one. You will learn how to strategically apply your negotiation skills as you navigate the process of securing a job offer; deciding which job opportunity is a good fit; and transitioning out of your PhD lab to begin a new chapter in your career. You will also learn how to execute each step with intention, clarity, and confidence.
In this session, you will learn how to thoughtfully choose your next job opportunity and successfully negotiate with both your current research advisor and prospective one. You will learn how to strategically apply your negotiation skills as you navigate the process of securing a job offer; deciding which job opportunity is a good fit; and transitioning out of your PhD lab to begin a new chapter in your career. You will also learn how to execute each step with intention, clarity, and confidence.
In this session, you will learn how to thoughtfully choose your next job opportunity and successfully negotiate with both your current research advisor and prospective one. You will learn how to strategically apply your negotiation skills as you navigate the process of securing a job offer; deciding which job opportunity is a good fit; and transitioning out of your PhD lab to begin a new chapter in your career. You will also learn how to execute each step with intention, clarity, and confidence.
After receiving an invitation to interview from your prospective postdoc lab you need to develop an interview game plan. Your ultimate goal is to demonstrate why you are a good fit for the position. A postdoc interview usually includes meeting and talking with the principal investigator and members of your prospective lab. In this session, you will learn how to strategically highlight your strengths during the interview process and prepare a postdoc job talk that is relevant to your audience and outlines how you will contribute as a scholar and potential colleague.
After receiving an invitation to interview from your prospective postdoc lab you need to develop an interview game plan. Your ultimate goal is to demonstrate why you are a good fit for the position. A postdoc interview usually includes meeting and talking with the principal investigator and members of your prospective lab. In this session, you will learn how to strategically highlight your strengths during the interview process and prepare a postdoc job talk that is relevant to your audience and outlines how you will contribute as a scholar and potential colleague.
When you apply for postdocs and other types of jobs, you typically need to submit a curriculum vitae and a cover letter as part of your application package. This session will teach you strategies to assemble an effective application package geared towards getting the position that you want.
As you start thinking about doing a postdoc, there are a few key questions you need to consider. What type of position will allow you to build the profile needed to be competitive for your ideal career? What skills, knowledge, experiences, and type of environment will support your success and productivity? Knowing this will help you prioritize what to look for in a postdoc and begin scouting for opportunities that fit your goals. This session will help you organize your postdoc search and leverage your mentoring network to find postdoc opportunities that match your career goals.
As you start thinking about doing a postdoc, there are a few key questions you need to consider. What type of position will allow you to build the profile needed to be competitive for your ideal career? What skills, knowledge, experiences, and type of environment will support your success and productivity? Knowing this will help you prioritize what to look for in a postdoc and begin scouting for opportunities that fit your goals. This session will help you organize your postdoc search and leverage your mentoring network to find postdoc opportunities that match your career goals.
The third video is a recording of a panel discussion moderated by SCL producer Rosa Veguilla on February 3, 2022. In this conversation, we asked the speakers follow-up questions about whether we can and should use CRISPR in the natural forest to combat climate change, and if so, what that might look like.
Coral reefs are truly magnificent ecosystems that support an abundance of marine life, and they are under threat. As climate change warms the oceans, corals become stressed by the heat and struggle to survive. Can modern genetic tools, like CRISPR-Cas9, help save them? Some scientists say it is our responsibility to make sure corals adapt to climate change.
Hearing loss, caused by the death of hair cells in the inner ear, is the third most common public health issue in the United States. Currently, there are no therapeutic strategies to restore hearing. In her thesis research, Dr. Amrita A. Iyer investigated the possibility of regenerating functional hair cells by reprogramming non-hair cells of the mouse inner ear. She found that overexpression of a single transcription factor, ATOH1, can successfully reprogram non-sensory cells into hair cells with typical characteristics in neonatal mice. However, a combination of three transcription factors - ATOH1, GFI1, and POU4F3 - was required to reprogram inner hair cells in 1-week old mice. Her findings provide a window into the developmental and gene expression requirements for regeneration of inner ear hair cells in mammals, and may inform future therapeutic strategies for hearing loss in humans.
Dr. Tshaka Cunningham received his PhD in molecular biology from Rockefeller University and completed postdoctoral training at the Institut Pasteur in Paris. He is the co-founder and CSO of Polaris Genomics, a precision behavioral health company. Dr. Cunningham is a leading advocate for diversity and representation in genomics and is Executive Director of the Faith-Based Genetic Research Institute.
This short film explores how Dr. Tshaka Cunningham, a molecular biologist and a Black man of faith, unites his personal and professional identities to advocate for community health through personal genomics. (Talk recorded in January 2018)Audience: General Public Student Researcher Educators Educators of H. School / Intro Undergrad Educators of Adv. Undergrad / Grad Duration: 00:08:47
The National Cancer Act was signed into law in 1971, declaring a “War on Cancer.” While cancer deaths have declined remarkably since then due to major advances in therapies, we are still far from eliminating cancer altogether. In her Share Your Research talk, Christina Cho discusses how we could make further progress in our fight against cancer by learning more about the tumor microenvironment and the role of the immune system on tumor growth. Her work focuses on the complicated functions associated with cancer-associated fibroblasts, which can both help and harm cancer cells.
More than 200 million people are infected with schistosomes, aquatic parasites that cycle between snails and humans, and cause the human disease schistosomiasis. Risk of contracting this disease is expected to rise in the coming years due to climate change, agricultural expansion, and population growth. In her Share Your Research Talk, Dr. Karena Nguyen provides an overview of the schistosome life cycle, including the points at which interventions can disrupt this cycle in order to reduce disease transmission. She then goes on to discuss her work modeling the impact of these interventions.
Intestinal villi are finger-like projections that line the small intestine, increasing surface area to help with absorption of nutrients. Injuries to the intestinal villi can cause a range of health problems, and can even be life-threatening. In this Share Your Research Talk, physician-scientist trainee Takahiro Ohara discusses his research on the molecular and cellular processes that drive recovery of intestinal villi. He describes the fetal-like state that cells on damaged villi take on, and how adaptive differentiation of these cells leads to proper villus recovery.
When we think of what makes two species distinct, we often think of their ability (or inability) to produce viable offspring. But is there anything we can learn from inviable offspring? In this Share Your Research talk, Maiko Kitaoka discusses her work on closely related Xenopus frogs. She reveals how examining hybridization between these species at the cellular level can provide insight into only the mechanisms that restrict cell division and development, but also broader patterns of how new species are able to evolve.
Unlike most animals, plants don’t have the option to run away when something is trying to eat them. Instead, they develop all kinds of chemical and structural defenses. But these defenses can be energetically costly, and plants’ ability to defend themselves can change over time and with the environment. In her Share Your Research Talk, Dr. Mia Howard discusses how soil microbes can influence defensive traits in goldenrod (Solidago altissima) at various stages of succession. Her work reveals that microbial communities from late succession soils can increase plant resistance to herbivory, and may even make plants less vulnerable to pests.
Exercise is like medicine for the mind and body, particularly in aging adults. Regular physical activity not only provides physiological benefits, it also reduces the risk of dementia, Alzheimer’s, and other declines in mental function associated with aging. In his Share Your Research Talk, Brandon Yates provides an overview how proper hydration during exercise can help maximize the health benefits associated with exercise. He also discusses why this is particularly important in older adults, who are often chronically dehydrated.
Saving The American Chestnut: A Case Study, we explore more deeply the complicated question of using biotechnology to make forests more resistant to climate change. We look to the story of the American Chestnut as an example of how scientists are trying to bring a once-abundant tree back from near extinction through genetic engineering. We also consider the budding genome-editing technology CRISPR Cas-9 as a more precise tool with great promise but also great uncertainty. Can we do it and should we do it?
Some people harbor deleterious mutations in disease-relevant genes, yet they are completely healthy. How are scientists trying to understand these so-called ‘genetic superheros’? In this Share Your Research talk, Dr. Mohamed El-Brolosy describes his thesis research in the model organism zebrafish. Dr. El-Brolosy found that genetic compensation to deleterious mutations relies on degradation of the mutant mRNA, which triggers upregulation of compensatory genes in a homology-dependent manner. These findings can inform strategies to better understand and treat genetic diseases, many of which have limited therapeutic options.
Solid tumors, such as those in the brain, can be deadly when they expand or spread to other parts of the body. Before they spread, tumors send out molecular messages within small membranous structures known as extracellular vesicles (EVs). The proteins and small non-coding RNAs inside EVs can help tumors evade the immune system and seed new sites of growth. In this Share Your Research talk, Dr. Luz Cumba García describes her thesis research on extracellular vesicles released by aggressive brain cancers called glioblastoma. Dr. Cumba García’s work helps scientists understand the EV profiles of different glioma subtypes, as well as how the messages inside EVs help them shut off the immune system.
In order to succeed in kindergarten and beyond, children must develop language skills within their home reading environment. This environment is often influenced by the reading ability of a child’s caregivers. In this Share Your Research talk, Dr. Paige Greenwood describes her doctoral research on the association between maternal reading ability and the development of the language brain network in children. Her work showed that lower maternal reading fluency is associated with higher language network connectivity to brain regions involved in cognitive control and semantics in children. These data suggest that if there is lower frequency or quality of engagement in the home reading environment, children’s brains may overcompensate to meet their language development needs.
Chronic liver diseases affect millions of people worldwide. By understanding how liver disease progresses, we may be able to identify new therapies that can protect the liver. Dr. Chrystelle Vilfranc studied the role of BRUCE, a protein that is known to be important in several cellular processes in our bodies, in liver disease. She found that the absence of BRUCE in mouse livers led to accelerated liver disease and higher rates of liver cancer when combined with a liver damaging compound. Furthermore, hepatocellular carcinomas that develop in the absence of BRUCE in the liver appear to have increased β-catenin activity. Loss of BRUCE may be a marker of early liver disease in humans, and rescuing BRUCE expression or activity may help stop or reverse disease in the liver.
Is it possible to define life using math? Dr. Alyssa Adams’s research seeks to answer precisely this question. In their Share Your Research talk, Dr. Adams introduces the concept of open-ended evolution, and describes how they have developed mathematical models to help us understand how biological systems can innovate within a changing environment. These studies could help us to identify living systems beyond our planet that may be vastly different from those we recognize on Earth!
What does a redwood forest look like, and sound like, in the wake of a devastating fire? See a forest in a new way in this new cinematic short from the Science Communication Lab. Walk through a fire-ravaged redwood forest with experts Beatrix Jiménez, a Land Stewardship Associate at the Sempervirens Fund, Ian Bornarth, a Bay Area-based photographer documenting post-fire recovery, and Alex Jones, the UC Santa Cruz Campus Natural Reserve Manager. Their observations make visible the forces of destruction and regrowth throughout the redwoods ecosystem.
Bat species are numerous and diverse, and are found in nearly every corner of the globe. Therefore, they serve as a valuable system to study the evolution of mammalian traits. Dr. Alexa Sadier collected field and museum samples from over 50 species of bats to ask how color vision evolved in this unique group of mammals. By looking at gene expression at multiple levels - DNA, RNA, and protein - Sadier determined that different bat species have color vision capabilities adapted to their diets, and UV vision has been lost independently in multiple species through regulation of all levels of gene expression. By “catching” evolution in action, Sadier’s research has revealed important insights into the mechanisms of evolution through trait loss.
Dr. Alex Moore provides an introduction to coastal wetlands, including the functional role they play in our world, as well as the many ways that these ecosystems are used for economic and recreational activities. Dr. Moore discusses the traditional approach to restoring coastal wetlands, and the ways that these efforts can fall short of restoring functional capacity in coastal salt marshes. Incorporating consumer interactions into restoration efforts may provide an opportunity to further improve wetland restoration. Moore finishes with a brief overview of work currently underway in coastal mangroves, another important wetland ecosystem.
Trees are magnificent organisms that have evolved very slowly over millions of years, making it hard for them to adapt to rapid changes in the environment. With climate change imminent, scientists estimate up to 25% of US forests will decline over the next three decades. In this film, four researchers ponder the question ”What can we do to help forests adapt to our changing planet?” The answer is, of course, not so straightforward, and leaves us thinking more deeply about the future of forest landscapes and how we can make them more resilient.
Nayak describes research she has done on methanogenic archaea – microorganisms that produce the potent greenhouse gas methane. One species of methanogens, Methanosarcina acetivorans, has unique chemical modifications on the enzyme it uses to produce methane. Dr. Nayak describes how she used CRISPR/Cas9 genome editing to determine that these modifications are used to protect M. acetivorans from environmental stress to ensure that the organism can support its metabolic needs in a changing environment.
Educational science videos are commonly used in undergraduate biology instruction, but what do we know about the student perspective on them? In this paper discussion and live Q&A, Dr. Laci Gerhart-Barley and Dr. Brittany Anderton present findings from their open-access paper “Engaging students through online video homework assignments: A case study in a large-enrollment ecology and evolution course.” Undergraduate biology educators will find a wealth of useful information on how to effectively implement science videos in homework assignments, develop assessment questions, and use the content in educational science videos to promote student engagement and learning of the process of science.
Synthetic cells can be used to teach us about the basic principles of life and evolution, and they hold promise for a range of applications including biomaterials and drug development. Dr. Kate Adamala narrates an introduction to this exciting field.
Meningioma is the most common intracranial tumor, with limited treatment options. In order to identify new therapies for meningioma, it is important to understand their underlying biology. In this Share Your Research talk, Dr. Abrar Choudhury describes his thesis research, which began by looking at DNA methylation patterns to better understand gene regulation in meningioma, leading him to identify the cell cycle proteins CDK4 and CDK6 as therapeutic targets.
Mentors shape our careers by guiding us through difficult decisions. But, how do you find a good mentor? In this series, Dr. Joanne Kamens advocates for the use of Peer Mentoring Groups as a method to provide and receive valuable mentoring opportunities. While working towards a common goal, group mentorship allows for an organic development of valuable experiences and accountability for your personal growth as you create a circle of mentors that will help throughout your career.
How do you go about forming a Peer Mentoring Group? In her second video, Kamens explains the logistics of forming a Peer Mentoring Group. First, you need to find 5-6 peers that share a similar problem. As you prepare to meet, you need to set the ground rules and provide structure to your meetings (e.g., provide agenda, assign a leader per meeting, decide on topics of interest, and provide curricula).
As Kamens explains, the commitment of the members is crucial for the success of the Peer Mentoring Group. In her third talk, Kamens overviews what are mentorship best practices while running a Peer Mentorship Group. From setting concrete content and activities to set up goals, these best practices will allow you to create an environment that will help you get feedback and find opportunities to grow.
Life on Earth evolved once - this means that all biological systems on our planet are rooted in the same fundamental framework. This framework is extremely complex and we have yet to fully understand the processes inside each living cell. One way of understanding complex systems is to break them down into simpler parts. This is the principle of engineering the synthetic cell: to use our current knowledge of biology for building a living cell with the least amount of parts and complexity. Synthetic cells can be used to teach us about the basic principles of life and evolution, and they hold promise for a range of applications including biomaterials and drug development. Dr. Kate Adamala narrates an introduction to this exciting field.
Gregor Mendel’s experiments with pea plants laid the foundation for our understanding of genetic inheritance. In this video, Shirley Tilghman tells the story of Mendel’s studies and how his data led to an understanding of how the information within genes is passed from generation to generation.
Rodolphe Barrangou studies beneficial microbes, focusing on the occurrence and diversity of lactic acid bacteria in fermented foods and as probiotics. Using functional genomics, he has focused on uncovering the genetic basis for health-promoting traits, including the ability to uptake and catabolize non-digestible carbohydrates. He spent 9 years at Danisco-DuPont, characterizing probiotics and starter cultures, and established the functional role of CRISPR-Cas as adaptive immune systems in bacteria. At NC State, he continues to study the molecular basis for their mechanism of action, as well as developing and applying CRISPR-based technologies for genotyping, building immunity and genome editing.
Jennifer Doudna and Emmanuelle Charpentier won the 2020 Nobel Prize in Chemistry for their development of a powerful gene editing tool known as the CRISPR-Cas9 system. In this short film, Doudna, Charpentier, and Martin Jinek, who was a post-doc at the time in Doudna’s lab, describe how their famous collaboration happened and share the story behind the influential experiments that led to their discovery.
Parasitic plants are important in natural ecosystems and in agriculture. Parasitism is a successful life strategy that has convergently evolved in all kingdoms of life.
Do students learn more with clickers and peer-discussion?
Bill Wood (University of Colorado, Boulder) describes the Knight et al. study, which looks at student learning gains in an active learning classroom that utilizes clicker questions and peer-discussion, similar to a think-pair-share.
Think-Pair-Share is an active learning technique that can be used in small or large enrollment courses to engage students and encourage them to practice scientific thinking skills. In think-pair-share, students think about their answer to a question, pair with a partner to debate their choice, and then share their answers with the class. In this video showing examples of think-pair-share in action, Kimberly Tanner (San Francisco State University) shares her experience using this method in classrooms of all sizes.
Clickers are Audience Response Systems that enable instructors to ask a multiple-choice question, poll students for an answer, and display the aggregated results to the class. In this video showing examples of active learning classroom models, Bill Wood (University of Colorado Boulder) describes how clickers can be used effectively to engage students.
How can one shift from a teacher-centered to a student-centered classroom model? What are the benefits of active learning for students and instructors?
What are the issues with traditional undergraduate biology education? What is the role of an educator in a 21st century college classroom? What is missing in the way we currently teach science in college?
We have an online Q&A (hosted on January 6th, 2021) discussing the benefits and limitations of preprints from the perspective of early-career scientists. Panelists included Jessica Polka, Elizabeth Silva (Associate Dean of Graduate Programs at UCSF and former editor at PLoS), and Kate Carbone (an industry postdoc).
Course Directors A. Malcolm Campbell, Kimberly Tanner, and Bill Wood talk about the reasons why we need to reform undergraduate biology education and why they got involved in the Scientific teaching Series project.
Dr. Harold Varmus talks to Dan Rather about his journey from literature major to scientist, and from the discovery of oncogenes to creating PLoS. Varmus reflects on his time as a researcher, as Director of the NIH, and on the importance of open communication in science. He ends by emphasizing why good science communication is important to engage more people in conversations about science.
How should we consider a journey through a career in science? How should we think of the future of science training? Few have given these kinds of questions more thought than Shirley Tilghman, a leading genetics researcher at Princeton University who also became president of that prestigious institution. In this far-reaching interview, Dr. Tilghman tells Dan Rather about her own path in science and how we need to rethink how we train and inspire budding scientists in a challenging career environment. This interview was filmed in 2013.
This video is a collaboration between the Lasker Foundation and iBiology.
Secretary Shultz has been addressing global crises inside and outside of government for decades. He now has his attention firmly focused on concerns over climate change and renewable energy. In a candid and provocative conversation, he explains to veteran journalist Dan Rather why this has become his cause and why he thinks his fellow Republicans need to take it seriously or risk being “mugged by reality.” Secretary Shultz is not looking to point fingers but instead create a framework by which elected leaders across the political spectrum can come together and work on solutions. Funding for this video was provided by the Carnegie Foundation.
Paul Nurse and Dan Rather have both spent their lives looking at the world and how it works, albeit from very different perspectives. Now the Nobel Prize winning geneticist and esteemed journalist come together for a frank and thoughtful conversation on the state of science and its role in society. Topics include climate change, GMOs, science education, how research spurs economic development, and Dr. Nurse’s own remarkably inspiring and surprising personal history. Funding for this interview was provided by the Lasker Foundation.
Eric Kandel won the Nobel Prize in Physiology or Medicine in 2000 for his work on the nervous system. Here, he discusses the mind, the brain, and his journey into a life of science.
This interview was filmed in 2008 for a series on the mind and the brain. This video is a collaboration between the Lasker Foundation and iBiology.
There are many challenges when it comes to addressing the destructive effects of climate change, and few people are better suited to address these challenges than Chris Field. A world-renowned researcher, Dr. Field understands the nuances and implications of the science. And as a gifted and trusted communicator who has the ear of the world’s diplomats, he can explain the urgency of action to policy makers and the general public. In this wide-ranging and thoughtful interview with Dan Rather, Dr. Field calmly but firmly explains what we know about climate change, what the stakes are, and what can be done about it.
How can instructors get started with active learning? What simple and effective active learning methods can easily be implemented in a course? Hear from instructors about their experience and see classroom demonstrations using think-pair-share and clickers.
Compare different pedagogical approaches and undergraduate biology classrooms. Reflect on how your teaching fits within the spectrum of educational models.
In the last few years, the term CRISPR has exploded on the global scene, and with it UC Berkeley professor Jennifer Doudna, one of the pioneers in the field, has emerged into the spotlight. From magazine covers, to news broadcasts, to social media, CRISPR is the rare scientific breakthrough that has captivated the interest of the general public. But what is CRISPR really? What are its implications now and into the future? What profound ethical questions are raised by this ability to so precisely and easily edit the genome? In a candid and far-ranging conversation with Dan Rather, Doudna leads viewers through a nuanced and captivating view of this new technology. And along the way she shares her own improbable journey into science and her lessons for others – especially young women – who want to follow in her footsteps.
Funding for this interview was provided by the Lasker Foundation.
The Dalai Lama has always had a keen interest in science. In this interview from 2008, Dan Rather and His Holiness talk science and what we can learn from the practice of meditation.
This interview was filmed in 2008 for a series on the mind and the brain. This video is a collaboration between the Lasker Foundation and iBiology.
Daniel Colón-Ramos began his life in science by being fascinated as a young boy by the unique environment of his native Puerto Rico. But in formal schooling, he found the excitement of discovery too often absent. Now a respected researcher at Yale University, Dr. Colón-Ramos keeps his boyhood enthusiasm for the awe and wonder of the natural world. He is eager to encourage scientific exploration and share his infectious spirit with his students and the larger world, as he does in this inspiring conversation with Dan Rather.
Jennifer Doudna tells the story of how studying the way bacteria fight viral infection turned into a genomic engineering technology that has transformed molecular biology research. In 2013, Doudna and her colleagues developed the CRISPR-Cas9 gene expression system that, when introduced into animal cells, makes site-specific changes to intact genomes. CRISPR-Cas9 is more precise, more efficient, and less expensive than other genome editing tools and, as a result, has facilitated a wide range of studies that were previously unachievable.
Since 1987, different versions of ImageJ have been used by scientists to analyze biological images. In this talk, Dr. Kevin Eliceiri provides an overview of ImageJ, explains how ImageJ has evolved through time, and demonstrates major functionalities of this open-source software.
The Scientific Community Image Forum is an online resource that helps scientists answer their bioimage analysis questions. In this talk, Dr. Anne Carpenter and Dr. Kevin Eliceiri encourage scientists to use the Scientific Community Image Forum when they have image analysis difficulties, and to familiarize themselves with the different tools that they can use to answer their questions.
In this series, Dr. Anne Carpenter and Dr. Kevin Eliceiri provide an overview of bioimage analysis. Pre-processing is the first step that follows image acquisition and will prepare your image by reducing the signal-to-noise ratio, applying appropriate filters to the image, and color extraction. Once you perform pre-processing, you’re ready for segmentation, the process of identifying individual cells or structures within an image. If appropriate for your dataset, you can use tracking to be able to link objects in space and time and measure speed, directionality, and cell division. The last step of bioimage analysis is to analyze the data by measuring different features like the number of cells or biological structures, or their size, shape, intensity or texture. Carpenter and Eliceiri finalize this series by providing tips on best practices that will aid scientists in properly analyzing their data.
In this series, Dr. Anne Carpenter and Dr. Kevin Eliceiri provide an overview of bioimage analysis. Pre-processing is the first step that follows image acquisition and will prepare your image by reducing the signal-to-noise ratio, applying appropriate filters to the image, and color extraction. Once you perform pre-processing, you’re ready for segmentation, the process of identifying individual cells or structures within an image. If appropriate for your dataset, you can use tracking to be able to link objects in space and time and measure speed, directionality, and cell division. The last step of bioimage analysis is to analyze the data by measuring different features like the number of cells or biological structures, or their size, shape, intensity or texture. Carpenter and Eliceiri finalize this series by providing tips on best practices that will aid scientists in properly analyzing their data.
In this series, Dr. Anne Carpenter and Dr. Kevin Eliceiri provide an overview of bioimage analysis. Pre-processing is the first step that follows image acquisition and will prepare your image by reducing the signal-to-noise ratio, applying appropriate filters to the image, and color extraction. Once you perform pre-processing, you’re ready for segmentation, the process of identifying individual cells or structures within an image. If appropriate for your dataset, you can use tracking to be able to link objects in space and time and measure speed, directionality, and cell division. The last step of bioimage analysis is to analyze the data by measuring different features like the number of cells or biological structures, or their size, shape, intensity or texture. Carpenter and Eliceiri finalize this series by providing tips on best practices that will aid scientists in properly analyzing their data.
In this series, Dr. Anne Carpenter and Dr. Kevin Eliceiri provide an overview of bioimage analysis. Pre-processing is the first step that follows image acquisition and will prepare your image by reducing the signal-to-noise ratio, applying appropriate filters to the image, and color extraction. Once you perform pre-processing, you’re ready for segmentation, the process of identifying individual cells or structures within an image. If appropriate for your dataset, you can use tracking to be able to link objects in space and time and measure speed, directionality, and cell division. The last step of bioimage analysis is to analyze the data by measuring different features like the number of cells or biological structures, or their size, shape, intensity or texture. Carpenter and Eliceiri finalize this series by providing tips on best practices that will aid scientists in properly analyzing their data.
In this series, Dr. Anne Carpenter and Dr. Kevin Eliceiri provide an overview of bioimage analysis. Pre-processing is the first step that follows image acquisition and will prepare your image by reducing the signal-to-noise ratio, applying appropriate filters to the image, and color extraction. Once you perform pre-processing, you’re ready for segmentation, the process of identifying individual cells or structures within an image. If appropriate for your dataset, you can use tracking to be able to link objects in space and time and measure speed, directionality, and cell division. The last step of bioimage analysis is to analyze the data by measuring different features like the number of cells or biological structures, or their size, shape, intensity or texture. Carpenter and Eliceiri finalize this series by providing tips on best practices that will aid scientists in properly analyzing their data.
In this series, Dr. Anne Carpenter and Dr. Kevin Eliceiri provide an overview of bioimage analysis. Pre-processing is the first step that follows image acquisition and will prepare your image by reducing the signal-to-noise ratio, applying appropriate filters to the image, and color extraction. Once you perform pre-processing, you’re ready for segmentation, the process of identifying individual cells or structures within an image. If appropriate for your dataset, you can use tracking to be able to link objects in space and time and measure speed, directionality, and cell division. The last step of bioimage analysis is to analyze the data by measuring different features like the number of cells or biological structures, or their size, shape, intensity or texture. Carpenter and Eliceiri finalize this series by providing tips on best practices that will aid scientists in properly analyzing their data.
In this talk, Dr. Anne Carpenter provides an overview of CellProfiler, a free, open-source software program for image analysis. CellProfiler helps scientists to identify and measure biological entities, process images, and export data for further analysis. Carpenter provides examples on how to use CellProfiler, and explains how CellProfiler can aid scientists in their bioimage analysis.
Modern microscopy produces large multi-dimensional datasets, which creates new challenges for data storage, processing and visualization. In this talk, Dr. Loic Royer uses a developing drosophila melanogaster embryo to explain how to solve some of the challenges produced by multi-dimensional microscopy datasets.
In order to understand an image of a biological sample and what it represents, one needs to understand its metadata. Metadata is the information behind the image that shows the experimental procedure, image acquisition settings, and the analysis performed on the data in order to obtain the represented image. Dr. Jason Swedlow explains what constitutes image metadata, and provides examples on how to catalog, organize, analyze, and share the metadata of biological images.
Microscopy is a key technology driving biological discovery. Nowadays, microscopy based scientific findings must be substantiated by quantitative image analysis. The discipline concerned with such quantification of biological microscopy images is called bioimage analysis. Dr. Christian Tischer walks us through the main concepts of a typical bioimage analysis workflow. He explains how to quantitatively interpret the content of microscopy images and how to automatically detect objects in images and derive object based measurements. He also emphasizes the importance of visual inspection and quality control of automated image analysis. Finally, he presents an overview of current bioimage analysis tools and communities.
How do we visualize biological samples? In this talk, Dr. Nico Stuurman provides an overview of the different tools, equipment, and software available to acquire an image of a biological sample using a light microscope, and the considerations one needs to take when using these tools. This lecture will allow scientists to understand the principles behind image acquisition in order to improve and optimize the analysis of their sample.
Manu Prakash always yearned to know the why and the how of things. As a boy in India, he spent endless hours playing outside with animals and making flammable artifacts in an abandoned lab in the basement of his home. Having the chance to explore his surroundings with open-ended curiosity, he learned to find the sublime in the mundane. Today, as a world-renowned researcher and inventor at Stanford University, he continues to be inspired by these childhood lessons, and is creating low-cost tools to empower people around the globe to go on their own journey of science and discovery.
Rebecca Calisi Rodríguez’s research on pigeons, like her life, is one of charting an original path. Her experiences as a Mexican-Italian-American woman, professor, artist and mother have provided her with fascinating and unusual perspectives to study the biology of parental behavior. And in so doing, she is redefining what it means to be a scientist.
There is ample evidence that race can be a major factor in health outcomes. But racial and ethnic minorities are underrepresented in clinical and biomedical research. In this series, Dr. Esteban Burchard talks about the consequences of this underrepresentation and what does it mean for equity in research and medicine. He also explains how race is used by your doctor to make critical decisions about your health, and discusses what happens if you don’t fit neatly in one racial box, and how does this impact the medical treatment. Finally, Burchard discusses how scientific breakthroughs often come when problems are approached from different perspectives, and the importance of improving diversity and inclusion in science.
There is ample evidence that race can be a major factor in health outcomes. But racial and ethnic minorities are underrepresented in clinical and biomedical research. In this series, Dr. Esteban Burchard talks about the consequences of this underrepresentation and what does it mean for equity in research and medicine. He also explains how race is used by your doctor to make critical decisions about your health, and discusses what happens if you don’t fit neatly in one racial box, and how does this impact the medical treatment. Finally, Burchard discusses how scientific breakthroughs often come when problems are approached from different perspectives, and the importance of improving diversity and inclusion in science.
There is ample evidence that race can be a major factor in health outcomes. But racial and ethnic minorities are underrepresented in clinical and biomedical research. In this series, Dr. Esteban Burchard talks about the consequences of this underrepresentation and what does it mean for equity in research and medicine. He also explains how race is used by your doctor to make critical decisions about your health, and discusses what happens if you don’t fit neatly in one racial box, and how does this impact the medical treatment. Finally, Burchard discusses how scientific breakthroughs often come when problems are approached from different perspectives, and the importance of improving diversity and inclusion in science.
In her third lecture, Zoghbi explores possible therapies for MECP2 disorders. First, using Deep Brain Stimulation (DBS), Zoghbi’s team together with collaborator Dr. Jianrong Tang were able to rescue learning and memory deficits, enhance neurogenesis, correct abnormal neural network activity, and improve MeCP2-linked gene expression changes in a mouse model of Rett Syndrome. Then, she discusses two approaches to normalize the MeCP2 protein in MECP2 duplication mice: by deleting the duplicated MECP2 gene in the genome, or by decreasing MECP2 mRNA levels using antisense-oligonucleotides. Even though these two approaches seem to rescue developmental issues caused by MECP2 duplication, titrating MeCP2 levels is required in order to avoid Rett-like symptoms caused by lowering the protein too much.
In her second lecture, Zoghbi explains how MeCP2 molecularly modulates neuronal function. Their studies uncovered a critical link between cytosine methylation, MeCP2, and the methylating enzyme Dnmt3a, in Rett Syndrome. They hypothesized that MeCP2 partially causes Rett-Syndrome symptoms by failure of reading methylated DNA marked by Dnmt3 and indeed showed that Dnmt3-dependent mCH plays a central role in Rett pathogenesis.
Dr. Huda Zoghbi’s work has provided insight into Autism Spectrum Disorders (ASD) by focusing on Rett Syndrome, a postnatal progressive neurological disorder. By studying the genetics of Rett Syndrome, her group made the seminal discovery of X-linked Methyl CpG-binding protein 2 (MECP2) as the gene that causes Rett Syndrome. Zoghbi’s group showed that the severity of the disease was highly dependent on the amount of functional MeCP2 protein expressed. Females, who carry one normal and mutant MECP2 allele typically suffer from Rett syndrome, but the amount of functional protein is influenced by X-chromosome inactivation, and girls with more cells expressing normal allele have milder features. Surprisingly, they also showed that duplications spanning MECP2 can cause a Rett-like progressive neurological disease, highlighting the importance of MeCP2 levels for neural functions. Zoghbi describes how these findings have spurred new research into how MeCP2 affects postnatal development and brain function.
As the COVID-19 pandemic escalated in the beginning of 2020, there was a need for the rapid dissemination of scientific information to understand everything from how the virus spreads, to how it affects the human body, to how the disease can be treated and prevented. Jessica Polka, Executive Director of ASAPbio, explains that, for this reason, the pandemic has inspired an increasing number of scientists to post their research papers on preprint servers. Publishing papers in traditional journals with formal peer review can take a lot of time. Posting manuscripts on preprint servers, on the other hand, can happen quite fast. But, considering that preprints do not undergo formal peer review before they are posted, is this prudent? Dr. Polka talks about how preprints experience their own crowd-sourced, informal peer review process through public commentary on social media and other venues by scientists and other experts, and this discourse can actually improve the quality of the paper over time. A major caveat of preprints is the potential for the media and the public, who may not be aware of the provisional nature of preprints, to disseminate erroneous or inaccurate information, and so, this requires proper education and training on what preprints are and how to interpret them.
In the cytoplasm of cells, thousands of tightly packed molecules and structures execute the numerous processes necessary to maintain life. Although there are many ways to study cellular processes, one of the simplest ways to understand the different parts of a cell is to visualize them. Dr. Sven Truckenbrodt sought to better understand the machinery of the neuronal synapse using fluorescence microscopy, yet he was limited by the physical properties of light. To circumvent the 250-nm resolution limit imposed by the photophysics of light waves, Truckenbrodt developed X10 expansion microscopy, based on the original concept of expansion microscopy invented in the Boyden lab. By uniformly expanding the volume of tissue by a thousand-fold using synthetic polymers (the same as those found in baby diapers!), this approach increases the distance between closely packed proteins, allowing them to be visualized with fluorescence microscopy. Truckenbrodt shares the story of the first time he used X10 expansion microscopy to clearly image synaptic vesicles, after studying them for years as a neuroscientist! He describes how he used X10 microscopy to characterize the precise localization of synaptic and cytoskeletal proteins that previously could not be visualized in detail. Truckenbrodt ends his talk by sharing how the X10 approach has been used by other research groups and encourages his viewers to consider applying this method in their own research to make new discoveries.
In his last lecture, Singer continues the story of the life and death of RNA. His lab has developed several more fluorescence microscopy techniques that let them study, in real time, the translation and degradation of mRNA. These techniques allow them to track when and where translation begins, how quickly a ribosome binds to a mRNA once it has reached its destination, how long the ribosome stays bound and how rapidly it adds amino acids to a growing protein chain. In addition, these techniques can be used to unveil the dynamics of RNA degradation. In an interesting twist, it turns out that for mRNAs that must be degraded during the cell cycle, their fate is decided at the time of their birth.
To understand the relationship between RNA localization and translation, it is necessary to visualize the movement of the RNA in real time. In his second lecture, Singer explains how his lab found an ingenious way to label RNAs in live cells and follow their movement. In the nucleus, RNA moves by diffusion and stochastically finds a nuclear pore to exit. In the cytoplasm, however, it is a different story. RNA, in a translationally repressed state, undergoes directed movement along the cytoskeleton. Once it reaches its destination, translation is activated. Singer’s lab showed that neuronal stimulation leads to ß-actin mRNA localization to dendritic spines, followed by translation, and stabilization of the synapse; events that are crucial for memory and learning.
In this series of lectures, Dr. Robert Singer explains how it is possible to follow a single mRNA molecule from its birth to its death. Singer begins by explaining that cell cultures are heterogeneous and analyzing single cells provides spatial and temporal information not available from bulk analysis. He outlines how his lab developed techniques such as fluorescence in situ hybridization (FISH) that have allowed them to measure gene expression in single cells. Using these techniques, they discovered that some RNAs localize to specific areas in the cell and RNA localization is linked to its regulation and function. For example, ß-actin mRNA localization to the leading edge of fibroblasts aids in cell motility. Singer’s lab identified “zip code” regions in mRNAs that are responsible for regulating mRNA localization.
In his second talk he reviews makeup of the plant cell wall and how hemicellulose, cellulose, and lignin can be broken down for use in aviation biofuel production. He describes the Joint BioEnergy Institute (JBEI) approach to maximize carbon efficiency at every step in the production of biofuels, from developing and feedstocks, deconstructing biomass, and use of microbes and enzymes to generate target intermediates for fuels. A major part of optimizing this process is the development of a one-pot process, in which conversion of biomass to fuel can be achieved in a single chamber.
Biofuels have been around for decades, but interest in them has grown considerably in recent years due to climate change. While they have the potential to provide a sustainable and renewable way to power our transportation systems, Dr. Blake Simmons points out that in order to become a viable replacement for fossil fuels, biofuels must also be efficient and affordable at global scales. In his first talk, he provides an overview of the advantages of using biofuels and walks through the biochemical processes required in order to convert biomass into usable fuels. He also discusses the ideal properties for advanced biofuels, the projected markets for these fuels in the coming years, and some of the key challenges associated with optimization of advanced biofuel production.
In his Part 3, Rutter emphasizes the challenge of mitochondrial protein synthesis. How do the components of the electron transport chain (ETC) assemble in the right stoichiometry at the right time? Rutter introduces the LYR family of proteins, which aid assembly of ETC components. LYR proteins interact with a common binding partner, the acyl carrier protein (ACP), via a unique fatty acyl moiety on ACP. Rutter’s group showed that ACP acylation is necessary for assembly of the ETC and activation of oxidative phosphorylation.
In Part 2 of his talk, Rutter describes his group’s work to unravel the relationship between the activity of the Mitochondrial Pyruvate Carrier (MPC) and the behavior of numerous cell types, including cancer and stem cells. His group found that forced expression of the MPC in multiple stem cell models led to reduced “stemness” and proliferative capacity, and that MPC inhibition could promote organoid formation in culture and tumor formation in vivo. These data indicate an important link between mitochondria, metabolism, and cell behavior.
Mitochondria are integral to the metabolism of eukaryotic cells, yet many of their properties are not fully understood. In Part 1 of this iBioSeminar, Dr. Jared Rutter lays out the foundational knowledge of mitochondrial structure and origin, and shares what is currently known about mitochondrial roles in metabolism, protein homeostasis, and signaling. He ends by highlighting a focus of his research group: to unravel the functions of uncharacterized mitochondrial proteins.
In his second talk, Peters presents evidence that cohesin is indeed necessary for genomic DNA to fold into loops. Long range DNA interactions such as loops can be detected using a technique called Hi-C. Using Hi-C, Peters shows that depleting cohesin removes DNA loops, while depleting the proteins that remove cohesin from DNA, results in bigger DNA loops. In addition, CTCF appears to recognize specific sequences that define the base of the loops. Incorporating all of this data, Peters describes a model in which DNA is extruded by cohesin to form a loop and the boundaries of the loop are determined by CTCF. Peters explains that many questions about the mechanism of DNA loop extrusion and its importance in cells remain to be answered.
It has been known for many years that the protein cohesin is necessary to join sister chromatids together before they are segregated during mitosis. Electron micrographs have shown that cohesin subunits form a ring complex which is thought to encircle the DNA keeping the chromatids together. When they need to separate during anaphase, the cohesin complex is removed by another set of proteins. In his first talk, Dr. Peters explains how observations that he and others made suggested that cohesin may have additional roles in the cell. For instance, cohesin is initially loaded onto chromosome arms at discrete sites and in much larger amounts than is needed for chromatid cohesion. Cohesin also was shown to co-localize on chromosomes with a DNA binding protein called CTCF. CTCF is known to regulate transcription by forming DNA loops. Peters explains that, taken together, these observations hinted at a role for cohesin and CTCF in folding DNA into loops to allow efficient packing of very large eukaryotic genomes into small cell nuclei, and regulating functions such as gene expression.
In his third talk, Patel explores the function of additional Hox genes in the development of crustacean body plans. Using CRISPR-Cas9 genome editing, his laboratory has characterized the expression and function of six of the nine Hox genes in Parhyale, and describes the combinatorial role of Ubx, abdA, and AbdB in the development of specialized appendages in this species, and how changes in the regulation of abdA is responsible for several morphological transitions during crustacean evolution.
In the second lecture, Patel describes the work of his lab to expand the studies of Hox gene function to other arthropods. Patel describes the development of specialized body parts in crustaceans, and describes the transition between feeding to locomotor appendages. Using the beach hopper, Parhyale, his laboratory, in collaboration with the laboratory of Michalis Averof, showed that Ubx controls the boundary and transition between feeding and locomotor appendages during development.
Homeotic (Hox) genes are transcription factors that dictate the development and compartmentalization (regionalization) of body parts in animals along the anterior-posterior (head to tail) axis. Using various insects and crustaceans, Dr. Nipam Patel studies how alterations in the expression of Hox genes could explain the evolution of specialized body parts in arthropods. Patel describes the spatially restricted patterns of Hox gene expression, explains the effects of Hox gene deletions, and how these phenotypes help us understand the manner in which Hox genes act to control the insect body plan. Taking a closer look at the pattern of the Hox gene Ultrabithorax (Ubx) in different insects, Patel summarizes the discovery that what drives changes in the number of wings during insect evolution is the not changes in the expression pattern of Ubx, but the regulation of its downstream gene targets.
In her second seminar, Parast explains the different models to study human placental development in-vitro. Scientists can derive induced pluripotent stem cells (iPSCs) from umbilical cord cells. Parast’s laboratory first differentiates the iPSCs into trophoblasts cells which can then generate the different cells found in the placenta. Her laboratory uses these placental cells to study developmental complications by comparing cells derived from normal pregnancies to cells derived from non-normal pregnancies (e.g. patients born from mothers with pre-eclampsia).
Dr. Mana Parast provides an introduction to placental development, the organ that every mammalian embryo needs for proper growth and development. The placenta derives from trophoblasts, embryonic cells located in the outermost layer of the embryo. Pre-eclampsia and other maternal factors can hinder placental development and therefore affect the development of the fetus. A better understanding on how defects associated with pregnancy disorders affect placental development could lead to novel therapeutics in the future.
What is the consequence of obesity in human health? Physically, obesity can result in lower mobility and sleeping disorders. But, in humans, the link between obesity and metabolic diseases isn’t straightforward. For example, not everyone that’s obese becomes insulin resistant. As O’Rahilly explains, the probability of an obese individual to have a metabolic disease is linked to the capacity of adipose tissue to store the extra fat. Mutations that decrease fat storage in adipose tissue increase the chance of metabolic diseases, like insulin resistance, even when the person is not obese.
Easy access to nutrients has contributed to the increase in obesity in the human population. But, what is obesity and why isn’t everybody fat? Dr. Stephen O’Rahilly provides a biomedical perspective of obesity, and evaluates which genes could potentially shift the balance towards obesity. As he explains, one becomes obese when the balance between energy intake and energy spent is shifted. Surprisingly, mutations that lead to obesity in humans aren’t in genes involved in metabolism and energy storage, but failure in satiety signals in the brain that result in people eating too much. The excess of energy intake over energy expenditure leads to obesity.
The severity of malarial disease is influenced by interactions between the parasite, the host and environmental factors. In her third talk, Mota explains how her lab used a mouse model to study the impact of host nutritional status on disease severity. When they compared infections in calorically restricted (CR) mice and freely fed mice, they found less reproduction of the malaria parasite and a lower parasite load in CR mice. This suggested that Plasmodium are able to sense and respond to host nutritional status. Mota describes how her lab identified a key Plasmodium kinase, KIN, that seems to regulate parasite response to nutrient availability and may provide a target for antimalarial drugs.
In Part 2, Mota goes into more depth about the liver stage of malaria infection. She reminds us that when Plasmodium parasites are transferred by a mosquito bite, they first travel to the liver. Once inside of a hepatocyte, a single malaria parasite will replicate and give rise to over 10,000 new parasites that go on to infect red blood cells and cause disease. For many years, this stage was called the silent stage as it was thought that malaria parasites were not detected by the host while in the liver. Mota tells us about data from her lab, and others, showing that the host innate immune response is, indeed, activated during hepatocyte infection. This immune response may play a role in modulating the host’s response to the blood-stage infection or future re-infection.
Malaria is currently responsible for about 500,000 deaths per year and is especially fatal to children under the age of 5 years. Two global eradication programs since 1950 have reduced the malaria burden significantly, however, progress has stalled in recent years. In her first talk, Dr. Maria Mota details the lifecycle of two malaria parasites, Plasmodium falciparum and P. vivax. The complex, multistage lifecycle makes it hard to diagnose and treat malaria. Mota explains that many attempts have been made to treat the disease with drugs but the malaria parasite very rapidly develops resistance. She describes how the recent development of drug combinations and a new vaccine, together with insecticide treated bed nets and improved early diagnosis, provide hope for better prevention and treatment of malaria in the future.
Almost every person in the world has been bitten by a blood feeding insect or arthropod, such as a mosquito or tick. Yet, most of us haven’t thought much about arthropod saliva. The molecules found in the saliva of blood feeders play a role in disease transmission and immune recognition. Therefore, it is important to better understand what makes up arthropod saliva. Dr. Mondragon-Shem begins her seminar by describing the phenomenon of red meat allergy, and how it was historically linked to tick bites. She then shares her research findings that confirm the presence of alpha-Gal sugar, the immunogenic molecule that leads to red meat allergy, in tick saliva. Her studies also identified protein candidates that are likely linked to alpha-Gal in tick saliva. Dr. Mondragon-Shem finishes her talk by describing how she has characterized the sugar molecules in the saliva of six species of blood feeding arthropods. This work has implications for better understanding disease transmission and immune recognition.
In 1953, Watson and Crick proposed a double-helical structure for DNA and suggested that it replicated in a semi-conservative manner. This method of replication was not universally accepted as correct, however. In this talk, Meselson recalls the events that led him to meet Frank Stahl and to plan and execute the now famous experiment proving that DNA does indeed undergo semi-conservative replication.
In her second talk, Lehmann focuses on the establishment of the dichotomy between somatic and germ line fate. She explains how Drosophila germ cells develop to become so different from the somatic cells that make up the rest of the embryo. Germ cell development depends solely on maternal transcripts from the egg, while development of the soma depends on new zygotic transcription. Lehmann describes how two different molecular strategies, precise spatially controlled protein degradation and complete interference with the mRNA transcriptional elongation process, are employed to prevent somatic differentiation, thus allowing germ cell specific gene expression to occur.
Very early in embryogenesis, germ cells, the cells that give rise to egg and sperm, are set aside from the somatic cells which give rise to the rest of the cells in our bodies. While germ cells are not necessary for survival of the individual, they are crucial for survival of the species. In her first talk, Dr. Ruth Lehmann explains that there are two mechanisms by which germ cells are specified in the early embryo; via germ plasm or via induction. Germ cells specified via either mechanism have in common the presence of germ granules; large, membraneless, ribo-nuclear particles. Interestingly, certain families of RNA regulatory proteins are conserved in germ granules across species. Lehmann describes work from her lab and others on the life cycle of germ granules in Drosophila, including how they are assembled, their interesting biophysical properties and how proteins and RNAs are organized within the granules.
To better understand how an entire embryo develops from a single cell, Dr. Philipp Keller and colleagues developed a technique to image and quantitatively reconstruct mouse embryogenesis from gastrulation through early organogenesis at the single-cell level. Keller’s lab developed an adaptive light-sheet microscope to follow the mouse embryo for 48 hours while it’s developing its germ layers (mesoderm, endoderm, and ectoderm), early tissues, and organs. By combining long-term high-resolution imaging, computational, and statistical analyses, they generated a dynamic fate map of the embryo. These open-access resources aid in the understanding of the dynamic cell behaviors that allow for proper growth and development of the embryo.
Corn is the backbone of the American food supply. Yet, about 10% of corn (equal to a field as big as the entire state of Florida!) is lost to disease and other types of crop stress each year. How can we make corn and other crops hardier so that we can grow more food, using less land and other resources? In her thesis research, Katie Murphy studies the synthesis of biochemicals produced by corn that help it survive stressful conditions such as drought and disease. She and her colleagues identified a new class of biochemicals called dolabralexins and showed that corn roots produce these molecules in response to drought and fungal infection, two common types of crop stress. She also determined that synthesis of dolabralexins and other terpenes influences the root microbiome of corn plants. Finally, Murphy’s work showed that dolabralexins have direct antifungal properties and identified the functional groups on dolabralexins that are necessary for this function. These findings may help scientists develop stress-resistant crops so that we are better equipped to feed a growing global population.
In his second talk, Kriegstein provides an overview of the use of cerebral organoids to study brain development and disease. Cerebral organoids are models that can be produced from induced pluripotent stem cells. Although organoids can contain the same broad categories of cell types found in the brain, organoids lack the structural, layer-like organization observed in the primary tissue. In addition, the gene expression profile is different between organoids and primary brain tissue. Nevertheless, although organoids do not reproduce all of the features of a developing human cortex, organoids can be a powerful model to study neuronal diseases and evolution, particularly when studying cells that cannot be found in animal models (e.g. oRG cells) or when scientists do not have access to primary brain tissue.
How do neurons develop to confer humans their unique brain functions? Dr. Arnold Kriegstein compares and contrasts the development of neurons from radial glial cells (RGCs) in mice and humans. In mice, RGCs give rise to most of the central nervous system’s neurons and glia and provide scaffolding for neurons to migrate. In contrast, human RGCs give rise to a unique set of cells, the outer subventricular zone radial glia (oRG) cells, which divide via mitotic somal translocation (MST). The oRG cells predominantly produce and guide the migration of the upper layer cortical neurons. Although rodents have oRG-like cells, these cells are more abundant in humans, and contribute to the large size of the human brain and possibly its unique function.
In her second and third videos, Iwasa provides an overview of the animation process. She shows different software that can be used to create molecular models (e.g. UCSF chimera), and illustrates the process of creating an animation and finalizing the video using software like Maya and Adobe After Effects. These videos will familiarize you with the process of creating an animation and show best practice techniques when using visual communication in biology.
In her second and third videos, Iwasa provides an overview of the animation process. She shows different software that can be used to create molecular models (e.g. UCSF chimera), and illustrates the process of creating an animation and finalizing the video using software like Maya and Adobe After Effects. These videos will familiarize you with the process of creating an animation and show best practice techniques when using visual communication in biology.
Scientists commonly use visual representation of data to show their results and ideas. In this seminar, Dr. Janet Iwasa provides an introduction to the field of molecular animation, and walks us through the process of using visualization tools to communicate scientific information. In her first video, Iwasa summarizes the common types of visualizations used in biology, explains the steps you should take to create a model figure, and summarizes key elements you should consider when creating your figures and models.
Matt Meselson and Frank Stahl were in their mid-20s when they performed what is now recognized as one of the most beautiful experiments in modern biology. In this short film, Matt and Frank share how they devised the groundbreaking experiment that proved semiconservative DNA replication, what it was like to see the results for the first time, and how it felt to be at the forefront of molecular biology research in the 1950s. This film celebrates a lifelong friendship, a shared love of science, and the serendipity that can lead to foundational discoveries about the living world.
In her third talk, Dr. Huber describes how a method known as RNA stable isotope probing (SIP) was used to characterize the metabolically active autotrophic microbes at an underwater vent at Axial Seamount. Dr. Huber’s group found that temperature influences the metabolic pathways, including the carbon fixation pathways, used by different organisms collected at the same vent. In addition, Dr. Huber’s group compared microbial activity across three vents and found that all three have different microbes that are active in a similar temperature environment. These findings suggest that subseafloor microbes prefer some environments over others and use different metabolic pathways in different environmental contexts.
In her second talk, Dr. Huber describes her research, which integrates microbiology, molecular biology, and ocean sciences approaches to characterize the microbial ecosystem below Axial Seamount, an underwater volcano off the coast of Oregon. Dr. Huber outlines how her group used environmental DNA and RNA sequencing techniques to analyze the crustal fluids (mix of ocean water & hydrothermal vent fluid) leaking from underneath the sea floor at three deep-sea vents. Her group determined that the metabolic potential of organisms was similar across vents (as indicated by DNA sequencing) but that there were larger differences in the “activity” of the microbes across vents (as indicated by mRNA profiling). Furthermore, Dr. Huber’s group identified vent-specific subseafloor microbial populations.
A mile or more below the surface of the ocean, microbes dominate the deep sea life. In this seminar, Dr. Julie Huber describes her research to better understand the microbial ecosystem in the rocky crust below the ocean floor. She begins the series by describing how reactions between seawater and the elements in ocean rocks enable chemosynthetic ecosystems to exist in the deep sea. She then introduces us to the tools scientists use to study microbial deep sea life below the ocean floor.
In his second part, Hasson explores how the ability of the storyteller to be coupled to and shape the neural responses of listeners is used as a tool to share memories across brains. Furthermore, the studies reveal the tight connections between remembering and imagining and expose the ways by which the storyteller’s perspective shape the audience point of view.
How does your brain change with each story that you hear? How can storytelling shape your memories? In this talk, Dr. Uri Hasson explores how brain activity is shared between listeners of the same story, and how those shared neural responses are coupled to and shaped by the neural activity in the storyteller’s brain. In his studies, Hasson observed higher coupling between listener’s and storyteller’s neural activity as a function of the ability of the listener to understand the story. As Hasson explains, efficient communication occurs when the storyteller’s and listeners’ brain responses are coupled.
Dr. Leland Hartwell started his scientific career studying a fundamental question in biology: how do cells know that they have everything they need in order to divide. By studying the morphology of temperature sensitive mutants in yeast, Hartwell identified many of the key regulators of the cell cycle. In this conversation, Hartwell talks to Dr. Sue Biggins about his Nobel Prize winning discoveries and the experiments that led to his seminal findings.
In his second talk, Haber explains in greater detail the molecular steps that take place during the repair of a DNA double strand break. It turns out that the process of mating type switching in S. cerevisiae requires site-specific cutting and repair of a yeast chromosome and this is an excellent model for studying DNA DSB repair. Working in this system and using techniques such as Southern blots, PCR and chromatin immunoprecipitation, Haber’s group was able to identify the proteins and enzymatic steps in DNA repair.
Dr. Haber begins his talk by explaining that broken chromosomes frequently arise during the process of DNA replication. In healthy cells, these double strand breaks (DSBs) are repaired by homologous recombination, an orderly process that preserves the genome. If the homologous recombination machinery is impaired, DNA truncations, translocations, and deletions often occur, resulting in genome instability and cancer. All mechanisms of homologous recombination have one common principal; the broken ends of the DNA are repaired by base pairing with a sequence that is identical or nearly identical and acts as a template for repair enzymes. Haber explains the general principles of homologous recombination and its critical role in maintaining genome stability.
In his second presentation, Haas shares an example of how cryocrystallography has aided structure-based drug design.
In his postdoctoral studies, David Haas set out to reduce radiation damage to protein crystals during X-ray crystallography. In 1970, he published a paper on his invention of macromolecular cryocrystallography – freezing crystals to extend their lifetime in the X-ray beam. The widespread use of the synchrotron beginning in the 1970s made cryo-cooling essential, and today nearly all protein crystal structures deposited in the international Protein Data Bank use this method.
In her second talk, Glaunsinger explores gene expression control by viruses like Kaposi’s sarcoma herpesvirus (KSHV), a frequent cause of cancer in AIDS patients. KSHV stimulates degradation of mRNA by encoding a nuclease, SOX, which is able to target a broad set of mRNAs for degradation yet cleaves them at specific sites recognized by a combination of RNA sequence and structure. Glaunsinger then describes how widespread mRNA degradation by viral nucleases such as SOX causes redistribution of RNA binding proteins in the cell and restricts mRNA transcription by RNA polymerase II. Thus, alterations to the rate of mRNA decay can have ripple effects in the cell that influence upstream events in gene expression.
Dr. Britt Glaunsinger provides an overview of virology, and describes how the study of viruses has guided the understanding of many fundamental cellular processes, from gene expression to cancer. These insights arise from studying how viruses manipulate and hijack cellular machinery during infection and viral replication. Viruses can use the host machinery to their advantage, altering the gene expression landscape of the cell to create an environment favorable for the infection to progress. As Glaunsinger explains, one way viruses alter gene expression is by affecting the messenger RNA (mRNA) degradation process. By increasing decay of cellular messages, viruses can decrease competition for access to the translation machinery and dampen the expression of immune stimulatory elements that restrict viral replication.
Coral reefs are a vital global ecosystem: despite comprising only 1% of the world’s oceans, they support more than 25% of marine life. In addition to supporting ocean life, coral reefs also support the survival of humans by providing habitat for fish and other seafood and protecting coastlines from erosion. Corals are complex organisms that rely on a symbiotic relationship between the coral animal, zooxanthellae algae, and microbes. To date, the role of the coral microbiome in coral health and disease hasn’t been extensively studied. In this Young Scientist Seminar, Maite Ghazaleh Bucher describes her thesis research at the University of Georgia in which she characterized the microbial communities of sick and healthy corals colocalized in the Florida Keys Reef during a disease outbreak in summer 2017. Using genetic analyses, Bucher found that the coral microbiome is relatively uniform in healthy corals, even among different coral species. In contrast, she found that the microbiomes of diseased corals are dissimilar, even among corals affected by the same disease. These data support an “Anna Karenina” hypothesis for the coral microbiome. In the second stage of her research, Bucher determined that the microbial communities of apparently healthy coral tissue on diseased corals exhibited an imbalance between “healthy” and “unhealthy” microbes. This finding could lead to a quantitative way to monitor the health of corals based on their microbial signatures. Bucher ends her talk with a call to action: we all have the power to reduce our impact on the planet, so that vital ecosystems like coral reefs can be protected. What can you do to support the survival of corals?
In their final talk, Walther and Farese explain how proteins are targeted specifically to the surface of lipid droplets. This has functional consequences since proteins at the surface of lipid droplets govern lipid droplet growth and hydrolysis, and some of these proteins are associated with diseases. Farese and Walther end their talk by describing a number of diseases or physiological conditions that are now recognized as resulting from mutations in genes encoding proteins involved in lipid droplet formation.
In Part 2, Walther and Farese explain in more depth how lipid droplets form in cells in an organized manner. Triglycerides and other neutral lipids are made in the ER membrane. They accumulate in localized regions of the membrane that grow towards the cytosol and eventually bud off into lipid droplets. Farese and Walther describe experiments from their lab and others that have identified a protein complex in the ER membrane called LDAF1/Seipin that regulates where triglycerides localize and grow into mature lipid droplets.
All life requires metabolic energy but energy supplies and demands change over time. For this reason, organisms have developed ways to store energy, predominantly as fat. Neutral lipids are packaged into lipid droplets, small organelles found in most eukaryotic cells and in some prokaryotes. Lipid droplets play a critical role in an organism’s physiology; too many lipid droplets can result in obesity and too few in metabolic disease. In their first video, Drs. Farese and Walther introduce us to lipid droplets and explain their importance in cellular biology.
DNA synthesis that occurs during repair is much less accurate than normal DNA replication. Using the yeast mating type switching system, Haber’s lab identified base pair substitutions, frame shifts and other mutations that occur when the newly synthesized strand dissociates from the template strand during homologous recombination. Interestingly, Haber found that sometimes the newly synthesized strand will “jump” to a related but divergent template, even on another chromosome, and then jump back to complete the repair. Further experiments showed that this happens because the repair polymerase falls off the template with a very high frequency. Understanding why this occurs may help us to decipher the complex chromosomal rearrangements associated with certain human diseases.
Esvelt’s second talk focuses on strategies to allow for the safe implementation of localized gene drive technologies that do not spread indefinitely. Daisy drive systems are made up of multiple elements connected like a daisy chain such that each causes the next to be preferentially inherited. They are designed to be self-exhausting by losing elements with each generation, thereby limiting spread. This technique has multiple applications such as removing an invasive species from one area without impacting the same species in its native habitat. Esvelt explains that daisy-drive stability might be tested in a species such as C. elegans where hundreds of generations can be grown in a short period of time. His lab is also developing technologies to reverse any unwanted genetic changes that might be introduced via gene drive. Once again, Esvelt emphasizes the importance of community input into any gene alteration projects. Although it does not currently involve gene drive, he uses the “Mice Against Ticks” project that seeks to prevent tick-borne diseases on the islands of Nantucket and Martha’s Vineyard as an example.
Evolution has selected wild organisms to be extremely well adapted to their environment. Because most genetic changes introduced by humans divert the resources of the organism to benefit humans, such mutations are typically eliminated by natural selection in the ancestral habitat. In his first talk, Dr. Kevin Esvelt explains how self-propagating CRISPR-based gene drives can be used to spread genetic alterations through wild populations, potentially impacting all organisms of the target species. Gene drives could be used to benefit public health, the environment, agriculture, and animal well-being. However, real-world use may incur ecological risks, and even research involving self-propagating gene drive systems may risk public trust in science and governance given the possibility of accidental spread. Esvelt explains how to minimize risk and discusses the importance of engaging communities in planning any projects which may affect them.
When an infectious disease outbreak happens, medical workers and public health officials mobilize, but there are also teams of researchers that snap into action. Dr. Tracey Goldstein and Dr. Koen Van Rompay are both actively involved in different initiatives to find answers surrounding the COVID-19 epidemic. They talk about the process of studying coronaviruses and other infectious diseases, the steps taken once an outbreak hits, and the ways in which this process could change for the better. The changing world we live in makes predicting outbreaks a challenge, but each one teaches us something new about how to understand and to respond to the next.
In his third talk, Clevers describes how organoids can guide our understanding of disease progression in cancer. In addition, using Cystic Fibrosis and cancer as examples, Clevers shows how organoids can be used to predict therapeutic outcome in patients.
In his second talk, Clevers shows how one can apply what we have learned from developing gut organoids to generate mini-organs for other epithelial tissues, like liver and lung. Clevers shows that these organoids have a similar expression profile as well as structural characteristics to those observed in real tissue. In addition, he shows how this technique can be used to generate non-mammalian organoids, like the development of venom gland organoids from snake venom gland tissue. As Clevers explains, such organoids can be used to discover possible novel therapeutics, including new anti-venom serum.
In his first talk, Dr. Hans Clevers provides a historical perspective on the discovery of adult stem cells in the gut. They identified a Wnt-dependent, rapid proliferating population of cells at the bottom of the crypt which seemed to be important for generating all epithelial cells in crypts and villi, and they hypothesized that these were gut stem cells. By using the Lgr5 gene as a marker, the Clevers’ lab confirmed that these long-lived cells were indeed the gut stem cells by showing that they were able to generate all of the cell types of the gut epithelium throughout life. Clevers characterizes the gut stem cells and its progenitors, and explains how his lab developed a technique to grow from a single stem cell an organoid or mini-organ, a structure that recapitulates the normal structure of the gut.
All general anesthetics act in the brain stem region to induce slow brain oscillations. Brown shares EEG spectrograms that clearly show that the brain response to anesthesia varies with age. Younger brains show strong oscillations while those of older brains show weaker oscillations. Interestingly, not all brains “age” at the same rate. By using EEG spectrogram to visualize brain dynamics, anesthesiologists can optimize drug dosage for individual patients. Brown closes his talk by presenting recent research suggesting that it may be possible to “turn the brain back on” after general anesthesia as a way to speed patient recovery.
What happens to your brain when you are under general anesthesia? Dr. Emery Brown explains that under general anesthesia your brain is not turned off but is very dynamic. Electrical oscillations in the brain can be recorded using an electroencephalogram (EEG). Brown shows how oscillations induced by anesthesia interfere with normal communication between different regions of the brain. By following oscillations of different frequencies, it is possible to monitor and adjust a patient’s level of unconsciousness under anesthesia.
In her third talk, Braybrook switches gears and highlights work from her lab on cell walls found in brown algae (seaweed). Although seaweed cell walls have much in common with plant cell walls, they do have some differences. Seaweed cell walls contain much less cellulose than plants, in fact, most of the wall is made of the gel matrix material, alginate. Braybrook’s lab studies the Fucus seaweed embryo to learn how changes in the rigidity or fluidity of the gel matrix impacts cell expansion patterns during development.
For a plant seedling to grow upwards and out of the soil so it can begin to photosynthesize, it must grow more in length than in width. Growth that occurs in one direction more than in another is called anisotropic growth. How do cells do this? In plants such as Arabidopsis, almost all of the initial increase in plant length or height is due to anisotropic growth of cells rather than cell division. In her second talk, Braybrook explains how her lab is using this system to study the role of cell wall components in determining anisotropic growth.
Cell walls are found throughout the tree of life (even in some animals!) and in most cases they serve similar functions of strengthening and protecting cells. Dr. Braybrook’s research focuses on cell walls found in multicellular organisms such as plants and brown algae. In her first talk, Braybrook explains that cell walls are made of cellulose which forms long strong fibers, a gel matrix such as pectin or alginate in which the cellulose is embedded, and cross-links such as hemicellulose or lignin that provide strength and hold the wall together. By improving our understanding of cell wall structure and biology, Braybrook’s research may help facilitate our use of plants and seaweed for biofuels and other products.
Dr. J. Michael Bishop tells us the story of his Nobel Prize-winning discovery of cellular proto-oncogenes. Bishop was studying how the Rous Sarcoma Virus (RSV) causes cancer in chickens by expressing the viral protein called Src. Together with Dr. Harold Varmus, Bishop discovered that the chicken genome normally expresses a homolog of the viral Src protein that they called cellular-Src (c-Src). This finding led them to the remarkable conclusion that RSV had incorporated a mutated oncogene version of the normal chicken c-Src protein, and, provided the first evidence that mutations in our own genes can be linked to cancer development.
In his second talk, Dr. Benfey dives even further into the cellular differentiation pathway of plant roots. He provides an explanation of the signaling pathway that activates positive feedback and feed-forward loops that impact the organization of cells as the root develops. He also covers how roots function as they spread through soil and how a chemical compound his lab identified can help roots grow through saline soil.
In his first talk, Philip Benfey gives an overview of root genetics and his work to identify genes that are involved in the process that takes a stem cell to a differentiated tissue. He explains how mutant Arabidopsis plants with shorter roots helped his lab understand how specific genes are expressed in plant roots, and how these genes affect root function. He reveals how a protein encoded by a gene called SHORTROOT moves from the vascular tissue to the endodermis to induce expression of another gene called SCARECROW. This whole complex is the on-off switch that causes certain root cells to divide and differentiate properly. Benfey also talks about how these genes can be used to change cell identity.
In Part 2 of his talk, DeBose-Boyd introduces a rare genetic disorder known as Schnyder Corneal Dystrophy (SCD). SCD is characterized by accumulation of cholesterol in the corneas of affected individuals, indicating that the genetic defect in SCD may affect cholesterol synthesis. Mutations in the UBIAD1 gene cause SCD – therefore, DeBose-Boyd’s lab sought to understand the role of UBIAD1 in regulation of cholesterol metabolism. They found that UBIAD1 acts as a sensor for levels of the metabolite GGpp, which enhances sterol-mediated ERAD of HMG CoA reductase. In the presence of GGpp, UBIAD1 releases HMG CoA reductase, leading to its proteasomal degradation. DeBose-Boyd’s lab also discovered a fascinating spatial regulation of UBIAD1, whereby binding of UBIAD1 to GGpp causes UBIAD1 to accumulate in the Golgi apparatus and away from HMG CoA reductase in the ER. Finally, his group found that the SCD-associated mutation N102S in UBIAD1 inhibits the interaction between UBIAD1 and GGpp, such that mutant UBIAD1 is unable to translocate from the ER to the Golgi in the presence of high GGpp.
Regulation of cholesterol synthesis is very important: cholesterol is a component of cell membranes and a precursor of steroid hormones and bile acids, yet high levels of cholesterol can be toxic to cells and can contribute to heart disease. Cells in our body obtain cholesterol one of two ways – by taking it up from the bloodstream (via low-density lipoprotein or LDL) or by synthesizing it intracellularly. In Part 1 of his iBioSeminar, Dr. Russell DeBose-Boyd provides an overview of cholesterol regulation with a focus on HMG CoA reductase, the rate-limiting enzyme of cholesterol synthesis. He describes how the effects of statins, drugs prescribed to lower LDL in the blood, are blunted due to the disruption of feedback control of HMG CoA reductase. In the presence of sterols, HMG CoA reductase protein stability is decreased. This sterol-accelerated degradation of HMG CoA reductase is dependent on the enzyme’s membrane domain in a process known as ER-associated degradation (ERAD). DeBose-Boyd describes his lab’s contributions to a model of HMG CoA reductase ERAD in which polyubiquitination of the enzyme in response to sterols is mediated by two proteins, Insig-1 and Insig-2, leading to its ERAD by the 26S proteasome.
Have you ever tried to catch a flying fly only to be frustrated by their ability to evade your efforts? Then you know that many insects are extremely agile fliers. In his three talks, Dr. Michael Dickinson uses aerodynamics, muscle physiology, and neuroscience to explain how flies fly.
In Part 1, Dickinson focuses on lift. How do insects generate the aerodynamic forces necessary to stay in the air? Dickinson explains that by studying high speed videos of flies in flight, it is possible to determine the motion of the wing at each moment in time and, from that information, determine the forces that the insect is generating during an entire wing stroke. Early studies of this type calculated that insects did not generate enough force to keep them in the air! So how do flies fly? To answer this question, Dickinson and colleagues built a large scale robotic model of an insect wing moving through a viscous solution. Video tape of these models showed that the wing can form a large vortex at its leading edge. This vortex augments the forces generated by the insect and provides enough lift to keep the insect in flight. By changing the angle of attack of the wing, the fly can change the size of the leading edge vortex and how much lift is produced.
In Part 3, Dickinson discusses how insects control flight. Insects have many sensors on their bodies and wings that detect odors, the polarization of light, body rotation, air movement, and more. All of this sensory information is taken in and integrated by the insect’s brain. The brain then regulates muscle function to perform the behaviors needed for the fly to survive in its natural environment. Dickinson and his colleagues have built “arenas” in which a fly can be tethered and visual cues can be used to make the fly think it is flying in a specific direction with a certain speed, or being attacked by a predator. Using high speed video, it is possible to measure the flies response to these visual cues. Amazingly, within 20 milliseconds of detecting a predator, a fly can integrate its response so that it completely changes flight direction and flies away from the perceived predator.
Dickinson’s second talk focuses on power. Small insect wings must beat very rapidly – much more quickly than can be controlled by the release and uptake of Ca2+ that typically regulates muscle contraction. Instead flies use two sets of stretch activated power muscles. The contraction of downstroke muscles stretches and stimulates upstroke muscles, and vice versa, allowing the insect to beat its wings very quickly. In addition to power muscles, insects have tiny steering muscles that connect directly to the wing and regulate wing deviation during the wing stroke. With a combination of high speed video and electrical recording, Dickinson demonstrates how these tiny muscles can change wing position and allow a fly to undergo its amazing aerial acrobatics.
In her second talk, Churchland outlines her group’s studies of the relationship between decision-making and action. She notes that in addition to methods to track neural activity, high-resolution videos of the decision-making process in mice provide valuable movement data. Using labeled calcium to visualize neural activity across the dorsal cortex, Churchland’s group finds that maps of the visual world are represented up to six times in each mouse brain! The Churchland group also found that neural activity appeared to be the same across novice and expert decision-makers. They developed a mathematical model to predict the influence of numerous variables on neural activity and found that movement-related variables accounted for a greater proportion of the variance in neural activity than decision-related variables. Specifically, spontaneous (non-instructed) movements had the greatest predicted influence on neural activity. They then validated their results at the single-neuron level using two-photon microscopy. Dr. Churchland ends her talk by highlighting a significant remaining question: what are the neural differences between novice and expert decision-makers?
How do brains make decisions? In this seminar, Dr. Anne Churchland tells us why understanding decision-making is important, and outlines common approaches to study decision-making in the lab using a variety of mammals. She describes findings that suggest accurate decision-making results from a combination of visual and auditory stimuli in both humans and rats, and tells of the discovery of an explore-exploit tradeoff that allows rats to respond optimally to changing environments. Dr. Churchland then outlines the major methods for tracking neural activity in the brain and shows how they have been used to determine that many brain areas are active during decision-making. She ends her talk with an overview of new directions in the field.
Christofferson also works on characterizing understudied arboviruses like Bunyamwera, Batai, and Ngari, all of which are orthobunyaviruses. First, in the laboratory, her lab studied the growth of these Orthobunyaviruses in-vitro and investigated a mouse model to determine the cross-reactivity of these viruses. In addition, in collaboration with scientists in Rwanda, Christofferson investigated whether Bunyamwera, Batai and Ngari circulated in the country, and caused disease in cattle. As Christofferson explains, a better understanding of the prevalence of viruses that affects the cattle may alleviate misdiagnosis and allows us to follow the possible emergence of newly detected viruses.
In her second talk, Christofferson uses the Aedes aegypti-Zika system to explain how mosquito-life traits can be used to understand the process of vector competence. Zika is an arbovirus that is transmitted to humans via the Aedes aegypti mosquito. Christofferson measures how much time it takes for a mosquito to become infectious after its initial exposure (extrinsic incubation period) in order to understand how mosquito age interacts with the viral fitness measure of vector competence. This is done in the context of a commonly used mathematical framework, vectorial capacity.
In this talk, Dr. Rebecca Christofferson provides an overview of arboviruses, arthropod-borne viruses, like dengue. Arthropods, such as mosquitoes, act as vectors to transmit diseases to vertebrates, including humans. Christofferson studies arthropod-virus-vertebrate interactions and how environmental factors affect disease transmission. For example, she explains how environmental factors, like changes in temperature and drought, affect the intrinsic ability of a vector to transmit a pathogen (vector competence).
In his Part 3, Chang reminds us that every lncRNA gene has its own set of DNA regulatory elements, such as enhancers and promoters. These regulatory elements can confer functionality to lncRNA genes. Chang shares the research story of a mysterious lncRNA known as PVT1, which is frequently co-amplified with the proto-oncogene MYC in human cancers. His group found that PVT1 promoter activity is inversely correlated with MYC expression – when one is up, the other is down. Finally, Chang shows that the PVT1 and MYC promoters compete for four enhancers located within the PVT1 gene locus.
In his Part 2, Chang introduces long noncoding RNAs, or lncRNAs. As their name suggests, lncRNAs are not translated into proteins, and initially their functions were poorly understood. Chang’s group has developed technologies to better understand the function of lncRNAs. For example, his lab characterized the protein partners that interact with Xist, a canonical lncRNA that mediates X chromosome inactivation. They found that the protein Spen is necessary for X chromosome silencing. Interestingly, Spen has likely been co-opted by mammalian cells to inactivate the X chromosome via viral mimicry.
In Part 1 of this series, Dr. Howard Chang introduces epigenomics, the study of DNA regulatory mechanisms that determine which genes are turned on or off in cells at specific times. The epigenome integrates signals from the environment to modify expression of the DNA blueprint inherited from an individual’s parents. Chang’s lab has pioneered techniques to map the landscape of chromatin, the complex of DNA, RNA and protein that organizes the genome and regulates gene expression. One example is ATAC, the Assay of Transposase Accessible Chromatin, which uses a bacterial transposase to mark open chromatin and identify genes that are likely turned “on”.
Chow gives advice on purifying DNA samples using magnetic beads and on determining the quality of your nucleic acid sample using an Agilent Bioanalyzer.
Chow gives advice on purifying DNA samples using magnetic beads and on determining the quality of your nucleic acid sample using an Agilent Bioanalyzer.
In the past decade there has been an amazing change in the efficiency of DNA sequencing. Using traditional Sanger sequencing, the human genome project took 20 years and cost $3 billion. Current next generation sequencing methods allow a human genome to be sequenced for $1000, in 48 hours! In this talk, Eric Chow explains the chemistry behind next generation sequencing, and describes how the next gen sequencers detect and display results. The most commonly used Illumina sequencers are image based and detect the addition of fluorescently labelled nucleotides. Chow also describes two different next generation sequencing technologies which provide benefits such as much longer reads but with downsides such as higher error rates. Chow finishes the talk with some insights into medical applications of next gen sequencing such as much less invasive prenatal testing or cancer detection.
Course Directors A. Malcolm Campbell, Kimberly Tanner, and Bill Wood talk about the reasons why we need to reform undergraduate biology education and why they got involved in the Scientific teaching Series project.
Before 1977, all life on Earth was classified into two groups: single-celled microorganisms and complex cellular life such as fungi, plants, and animals. A seminal discovery in 1977 rewrote the tree of life and introduced a whole new domain of organisms known as the archaea - mysterious microbes that are genetically distinct from bacteria. Fast forward to the 21st century, and again new discoveries about archaea are leading scientists to reshape the tree of life and rewrite the evolutionary history of complex organisms. Dr. Dipti Nayak introduces the fascinating organisms known as archaea and explains how they are helping scientists answer the question Where do we come from?.
What if we could understand the human cell in such detail that we could paint an accurate representation of a cell’s molecular organization? In this lecture, Dr. Manuel Leonetti outlines the different genome-wide approaches that scientists are using to build a complete map of the human cellular architecture. Understanding protein networks and localization could aid our quest to understand human biology and disease.
Michael Alley has been teaching scientists and engineers how to design presentation slides and deliver effective scientific talks for over three decades. In this three-part lecture, you will learn (a) how to design your PowerPoint or Keynote slides, (b) how to organize your talk, and (c) how to confidently deliver your research seminar. This series will help trainees and research scientists alike improve their presentation skills.
Michael Alley has been teaching scientists and engineers how to design presentation slides and deliver effective scientific talks for over three decades. In this three-part lecture, you will learn (a) how to design your PowerPoint or Keynote slides, (b) how to organize your talk, and (c) how to confidently deliver your research seminar. This series will help trainees and research scientists alike improve their presentation skills.
Michael Alley has been teaching scientists and engineers how to design presentation slides and deliver effective scientific talks for over three decades. In this three-part lecture, you will learn (a) how to design your PowerPoint or Keynote slides, (b) how to organize your talk, and (c) how to confidently deliver your research seminar. This series will help trainees and research scientists alike improve their presentation skills.
Microglia are the primary immune cells in the central nervous system. In the brain, they play central roles in proper development and function, as well as dysfunction and disease. In her first talk, Dr. Beth Stevens provides an overview of the many ways microglia cells operate, and how they can both harm and protect the brain. Fairly recent advances in the study of microglia through imaging have allowed researchers to identify different microglia states and study their dynamic roles at different stages of development.
Dr. Stevens dives deeper into the mechanisms that allow microglia to shape the network of connections between neurons in the brain. She provides an introduction to the role of microglia in synaptic pruning, the process of eliminating extra synapses in healthy developing brains. She then goes on to explain how the reactivation of this process affects aging and diseased brains.
Single cell sequencing, as the name implies, allows researchers to examine the genomic information for individual cells. This provides an opportunity to examine cell-to-cell differences and identify cell subtypes, which provides insight into how specific cells function within and respond to their environment. Dr. Eric Chow begins his talk with an overview of single cell sequencing with a focus on RNA. He then goes on to outline the predominant approaches, including plate-based, microfluidic-based, and combinatorial indexing methods. He finishes by addressing approaches to single cell analysis that don’t rely on RNA, including methods that use DNA, proteins, and antibodies. He also reviews some of the benefits and limitations of analysis at the level of individual cells.
The nucleosome is the central organizing structure of the eukaryotic genome. It consists of DNA wrapped around histone proteins. Dr. Karolin Luger shares her discovery of the three-dimensional structure of the nucleosome using X-ray crystallography, which provided a deeper understanding of chromatin organization.
Many of us are used to seeing cartoons of cells with organelles shown as static, isolated structures.
Voeltz explains how her lab used a BioID strategy to identify some of the proteins found at membrane contact sites between the ER and endosomes; a difficult task given the transient nature of contact sites.
Eukaryotic cells have many different membrane-bound organelles with distinct functions and characteristic shapes. How does this happen? Dr. Tom Rapoport explains the important role of protein sorting in determining organelle shape and function.
The ER is a vast network that includes different domains with different functions. The rough ER is made of ribosome covered membrane sheets and is involved in protein translation.
Dan Littman discusses the opposing roles of Th17 cells. They protect mucosal surfaces from infection with bacteria and fungi, but they can also cause autoimmune inflammation.
Littman explains that different commensal microbes in our gut elicit different T cell responses - either pathogenic or non-pathogenic.
In mammals, sex is determined by a pair of unequal sex chromosomes. Genetically male mammals have an X and a Y chromosome while genetically female mammals have two X chromosomes. The X chromosome is many times larger than the Y chromosome. To compensate for this genetic inequality, female mammals undergo X chromosome inactivation in which one of the X chromosomes is randomly chosen to be silenced. X chromosome inactivation has been studied for over 50 years both because it is a physiologically important event and because it is an excellent model for studying epigenetic silencing of genes by long non-coding RNAs. In her first talk, Dr. Jeannie Lee gives an overview of the steps a cell must go through during X inactivation. These include “counting” the X chromosomes, deciding which X chromosome to inactivate, initiating the inactivation and spreading it across the chromosome, and finally maintaining inactivation of the same X chromosome for the rest of the life of the organism.
Lee elaborates on the early steps of X inactivation. Very early in development, cells “count” the number of X chromosomes and decide if one needs to be inactivated, and if so which one. There is a region of the X chromosome called the X inactivation center which is enriched in long non-coding RNAs (lncRNAs). Lee explains how she and others showed that by sensing the ratio of two specific lncRNAs the cell can determine how many X chromosomes are present. Further studies showed that two different lncRNAs are responsible for randomly determining which X chromosome will be inactivated. Finally, she discusses the hypothesis that the allelic choice mechanism depends on a transient chromosomal pairing event that occurs at the beginning of the dosage compensation process.
Lee describes how X inactivation is nucleated and spreads across the X chromosome. The Xist lncRNA is known to be necessary and sufficient for X inactivation. Lee describes experiments that identified the factors that tether Xist to the X chromosome and showed how Xist spreads to cover the entire X chromosome. She then goes on to explain that Xist blocks transcription in three ways: 1) Xist recruits factors that repress transcription via epigenetic modification such as histone methylation 2) Xist repels factors that open chromatin preparing it for transcription and 3) Xist changes the 3 dimensional organization of chromosomes. Lee ends with a model of our current understanding of the complex but critical process of X chromosome inactivation.
Dr. Susanne Heck begins her talk by explaining why we might choose to use mass cytometry rather than other types of flow cytometry. Traditional flow cytometry is typically limited to the detection of about a dozen parameters in one sample due to overlap between the emission spectra of fluorochromes used to label antibodies. Mass cytometry, on the other hand, allows for the detection of up to 50 parameters in one sample because antibodies are labelled with metal isotopes and separated based on their mass. Heck goes on to explain which metal isotopes are typically used for mass cytometry and why, and she describes how a mass cytometer functions. She finishes by running through an example of using mass cytometry to perform functional phenotyping on human bone marrow cells.
The expansion of lungs for oxygen uptake is facilitated by lung surfactant. The groundbreaking discovery of this substance was made by Dr. John Clements. In this Discovery Talk, Clements details his scientific journey, touching on his early research, the resistance he encountered in the field, and the discovery of lung surfactant, which has saved millions of neonatal lives.
There are many processes and signals in cells that must be turned on and off, sometimes very quickly. How is this done? One important way is via post-translational modification of proteins such as phosphorylation or dephosphorylation. In her first talk, Dr. Anne Bertolotti introduces us to protein phosphatases, the enzymes that remove phosphate from proteins and work in opposition to protein kinases. She gives a brief history of the early experiments that showed that phosphatases are vital to regulating the stability, localization and interactions of many proteins. Bertolotti also describes more recent work demonstrating that protein phosphatases are split enzymes with a catalytic subunit and a subunit that determines substrate specificity. This selective subunit makes phosphatases exquisitely specific and attractive targets for drug development.
Bertolotti’s lab has had a long time interest in understanding protein folding and the role of misfolded proteins in neurodegenerative disease. In her second talk, Bertolotti explains how her lab found that selectively inhibiting the dephosphorylation of eIF2⍺, a translation initiation factor, led to a reduction in protein synthesis. Decreasing protein synthesis allowed cells to “catch up” with the degradation of misfolded proteins that may accumulate as a result of cell stress. Her lab went on to show that a selective small molecule phosphatase inhibitor had therapeutic effects in a mouse model of Charcot-Marie-Tooth disease; a disease that results from the accumulation of misfolded protein in the ER. This exciting result suggested that targeted inhibition of protein phosphatases may have therapeutic potential for neurodegenerative diseases.
Bertolotti describes a platform developed by her lab that has allowed them to rationally identify selective protein phosphatase inhibitors. Using this platform her lab identified a novel small molecule phosphatase inhibitor that blocks the accumulation of misfolded proteins in the cytosol or nucleus and showed the therapeutic effects of the molecule in a model of Huntington’s disease.