Columbia University Bio Bytes

In which Martin Chalfie, a professor of Biological Sciences at Columbia University and Nobel laureate recognized for his contribution to the development of green fluorescent protein (GFP), and Sophia discuss the applications of GFP and his current research on the development and function of touch receptor neurons (TRNs) using the nematode Caenorhabditis elegans. Dr. Chalfie highlights the versatility of GFP as a tool for studying biological processes, including the development and function of neurons. He explains the regulation of TRNs by transcription factors and transduction channels and how studying their development and function can provide insights into sensory perception.

Description: In which Sophia speaks with Carol Prives, the Da Costa Professor of Cell and Molecular Biology at Columbia University and a member of both the National Academy of Sciences and the American Academy of Arts and Sciences, about her journey researching the structure and function of the p53 tumor suppressor protein. She delves into the importance and regulation of p53, including its relationship with kinases, Mdm2, and the Mevalonate pathway.

Editorial Note: During the discussion regarding the mevalonate pathway, the listener should note that genes in this pathway had reduced expression when mutant p53 levels were reduced. Pathway genes, themselves, were not mutated.

In which Ian Maze, professor of Neuroscience and Pharmacological science in the Icahn School of Medicine at Mount Sinai and an investigator of the Howard Hughes Medical Institute, and Vaibhav discuss the intersection of chromatin biochemistry and neuroscience. Ian describes the diverse mechanistic functions of neurotransmitters, especially as they pertain to modifying histones and other proteins. He also describes Mount Sinai's Center for Neural Epigenome Engineering, of which he is the inaugural director, and provides advice for young scientists. 

In which Neil Vasan, assistant professor of medicine and medical oncologist at the Columbia University Irving Medical Center, and Vaibhav discuss the biochemistry and structural biology of kinases, as well as their salience in cancer development and progression. Neil tells the story behind his critical discovery of hyper-activating double mutations cooccurring in cis on PI3K alleles, discusses his group's use of deep mutational scanning in elucidating mechanisms of drug resistance and disease pathogenesis, and describes his efforts to illuminate the dark phosphoproteome. As well, he discusses how proteomics complements genomic approaches to understanding cancer and provides advice for aspiring physician-scientists. 

In which Darcy Kelley, Harold Weintraub Professor of Biological Sciences, and James discuss Xenopus as a model organism for understanding the biology of behavior and evolution of neural circuits. Professor Kelley describes several ways in which contemporary methods like single-cell RNA sequencing and optogenetics are helping us understand the true connection between neurobiology and behavior. Additionally, she provides insight on how young scientists can effectively develop themselves after initial exposure to research. 

In which Harris Wang, associate professor of Systems Biology at the Columbia University Irving Medical Center, and Vaibhav discuss the application of systems and synthetic biology to the study of microbial communities. He describes the motivation and application of many of his group's seminal contributions (MAGE, CAGE, MaPS-seq), the various use cases of synthetically minimal genomes and engineered bacteria, and closes with some advice for young scientists and trainees. 

In which Adam Bass, oncologist and inaugural director of the Columbia Center for Precision Cancer Medicine, discusses the relevance of genomic science and treatments informed by sequencing in modern cancer medicine. Among other things, Vaibhav and Adam discuss current standards of care involving sequencing, the importance of first-principles understanding and research in advancing medicine, and what the future of precision medicine might look like. 

In which Albert Keung, Assistant Professor in the department of Chemical and Biomolecular Engineering at North Carolina State University, shares many insights on Synthetic Biology. He touches on synthetically perturbing the chemical makeup of chromatin, designing and using DNA databases to store digital information, and the challenges and promise associated with developing cerebral organoids. 

In which Aaron speaks with Zach Abbott, PhD, about his company ZBiotics. ZBiotics is a biotechnology start-up that is focused on engineering microorganisms for consumer benefit. Aaron and Zach talk about the company’s current product, a genetically engineered probiotic designed to breakdown acetaldehyde, a toxic byproduct of alcohol. Additionally, Zach offers insight on his transition from completing a PhD to the biotech start-up space.

In which Vaibhav speaks with Dr. Mohammed AlQuraishi, an Assistant Professor of Systems Biology at the Columbia University Irving Medical Center, about using machine learning to predict protein structure. Among other things, they discuss the direction of algorithmic development in computational structure prediction, from neighborhood-based assembly of peptide fragments to modern applications of Deep Learning in structural modeling. They discuss the features of physical priors and discuss approaches in computationally optimizing protein-energy state predictions, taking into account the difficulties associated with the many local minima in an energy function. Throughout this discussion, Mohammed contextualizes the intuition behind the methods used by Deep Mind with their developments of AlphaFold.

In which Vaibhav speaks with Dr. Alison Taylor, an Assistant Professor of Pathology and Cell Biology at the Columbia University Irving Medical Center, about her research on the role of aneuploidy (abnormal numbers of chromosomes) in cancer. Among other things, they discuss the basic mechanisms of aneuploidy, the ways in which it can favor cancer development, and contemporary approaches in chemically targeting aneuploid cells. Alison explains her group's models for studying aneuploidy and their new computational genomics efforts as well. She concludes by discussing ongoing projects in her lab and some pressing questions about genome integrity in cancer initiation and progression. 

In which Aaron speaks with Alex Chavez, MD-PhD about antiviral drug development. They discuss chemical strategies for protease inhibitor development and the details and rationale of a novel assay that allows for early validation of candidate drugs. Additionally Alex discusses newer collaborations he is engaged in to build cellular resistance to damaging radiation. 

In which Josh speaks with Stavros Thomopoulos, PhD about biomechanical engineering at the tendon-bone interface. Dr. Thomopoulos is the director of the Caroll Laboratories for Orthopedic Surgery and the Vice Chair for Basic Science Research in Orthopedic Surgery at the Columbia University Irving Medical Center. Among other things, they discuss the challenges of attaching a tendon to a bone and stem cell-based regenerative medicine to improve healing in orthopedic injuries, such as those to the rotator cuff.

In which Josh explores the intersection of molecular biology, structural biology, and cardiology with Dr. Andrew Marks. Dr. Marks is the Chairman of the Department of Physiology at Columbia Medical School, the Founding Director of the Wu Center for Molecular Cardiology, and a professor of Physiology and Cellular Biophysics and Medicine. Among other things they discuss his critical development of the rapamycin coated drug eluting stent, his past and current work on Ryanodine receptors, and the multi-system impact of defective Ryanodine receptors. 

In which Vaibhav and Dr. Aaron Viny (a clinician scientist and assistant professor at Columbia) discuss the role of Cohesin complexes in 3D genome organization and how spatiotemporal irregularities in higher order genetic structures lead to blood cancers. They talk about the importance of linage commitment and how a disorganized genome can prevent it. Aaron concludes with a discussion of his experience as a physician-investigator and  meeting (now president-elect) Joe Biden. 

In which Vaibhav and Shawn Liu (The Joan and Paul Marks, MD ’49 Assistant Professor of Physiology and Cellular Biophysics at CUIMC) speak about the specifics of epigenome editing, from selecting the right model cells, to tool design, to loci considerations for editing experiments and much more. They also touch on how neurons are methylated during memory acquisition and the potential for in vivo neuroepigenome editing. Find out more about Shawn's work here: https://epibrain.info

In which Dana speaks with Vaibhav and Jason about the principles of single cell analysis and informatics challenges associated with it. Among other things, they discuss manifolds and data topology, Bayesian approaches and considerations in prior distribution selection in biology, matrix factorization and imputing missing cell states with graphical walks through phenotypic space, and the utility of diffusion components when  Principal Component Analysis is insufficient. Dana concludes with some advice for young people interested in Systems and Computational Biology.

In which Vaibhav and Dr. Stockwell talk about how using small molecule screening helped uncover pioneering details about Iron influenced cell death (Ferroptosis), the therapeutic context for Ferroptosis, and ligand prediction with computational chemistry. They conclude with some discussion about Dr. Stockwell's current collaborative SARS-CoV2  antiviral efforts. 

In which Dr. Lappalainen speaks to Vaibhav and Mona about a variety of topics including her latest paper in Science, the various considerations one needs to make when interpreting statistical genomic data, and a graphical representation of genomes as opposed to the traditional linear model. 

In which Vaibhav, Jason, and Professor Xuebing Wu discuss the mechanism and applications of CRISPR-Cas13 and how deep learning might be used to model a unified gene regulatory network. 

In which Vaibhav and Professor Racaniello continue to speak about the epidemic timeline, the use and biology of Anti-Malaria drugs against COVID-19, single cell and CRISPR based antiviral studies, and other topics, like how strong immunity to the virus is (once developed).  

In which Vaibhav speaks to Vincent Racaniello, professor of Virology at Columbia University, about the science behind the current Coronavirus (SARS-CoV-2). Among other topics, they discuss the origins of the virus and the rationale behind current retroviral drug based approaches to treat patients. 

In which Vaibhav and Dr. Azizi continue their discussion on using machine learning to integrate various data modalities into sensible probabilistic and statistical models to better understand cancer genetic networks. 

In which Vaibhav and Dr. Elham Azizi discuss the role of machine learning, AI, and data modeling in cancer biology. 

In which Vaibhav and Jason talk to Dr. Pe'er about the central goals of Systems Biology, the projects that he's most excited about, and what sorts of coursework students should complete to prepare themselves for getting into the field

In which Vaibhav and Jason talk to Dr. It'sik Pe'er, Associate Professor of Computer Science with cross-affiliation in the Systems Biology department, about his current projects and the emergence of computational biology

In which Vaibhav and Jason talk to Dr. Sternberg about how computational power is advancing his work with CRISPR

In which Vaibhav and Jason speak with Dr. Sam Sternberg about his work at the forefront of CRISPR tools development 

In which Vaibhav speaks to Dr. Chao Lu, Assistant Professor of Genetics and Development at CUMC, about his work in the field of Epigenetics and  how computation is accelerating progress in discovering novel targets for therapy. 

In which Miriam Interviews Dr. Raul Rabadan about the role of computing in Systems Biology, his journey as a theoretical physicist from CERN to the Institute for Advanced Studies in Princeton,  to Columbia's Systems Biology Department, and why now is the time to be excited about Systems Biology. 

In which Miriam speaks to Dr. Nicholas Tatonetti, Herbert Irving Assistant Professor of Biomedical Informatics, about his research regarding EHR, his children's book Toshi Builds Consensus, and much more! 

In which Miriam, Allison, and Vaibhav go over similarities and differences between Systems Bio, Synthetic Bio, and Computational Bio, and Bioinformatics.

In which we introduce ourselves, give a brief overview of Systems Biology, and discuss the potential of the field.