Physiology: Modern Cell Biology Using Microscopic, Biochemical and Computational Approaches
This course is at the forefront of new tools — molecular, computational, biophysical — as it prepares students to tackle emerging biological questions.
Directors: Cliff Brangwynne, Princeton University; and Amy Gladfelter, Duke University
Course Description
The MBL Physiology course is a platform for collaborative discovery across disciplines. For over a century, the Physiology course has been a crucible for groundbreaking biological discoveries—including the Nobel prize-winning discovery of cyclin B—by evolving to embrace and create new tools and approaches. The next phase of the Physiology course moves beyond its traditional strengths in quantitative cell biology, to encompass biological mechanism “at scale”, Levering High Dimensional datasets and advanced computational approaches incorporating AI/ML. Building from its world-renowned foundation in quantitative microscopy-based experimentation, the Physiology course is being reimagined as an engine for the development, testing, and deployment of cutting-edge technologies that combine imaging, omics, and AI to decode the complexity of living systems and unlock the next wave of discoveries
The Physiology course was founded in 1892 by Jacques Loeb, in the early era of cell biology, when a key focus was on understanding the physicochemical nature of cells, using various marine organisms as models (“Physiology 1.0”). Half a century later, the Physiology course became a hotbed for the biomolecular revolution, hosting luminaries including Rosalind Franklin, James Watson, Sydney Brenner, Matt Meselsen, and Frank Stahl. Decoding the central dogma, together with steady advancements in electron and light microscopy ushered in a new age of cell biology (Physiology 2.0), focused around discovery and characterization of the molecular parts (e.g. Cyclin, Kinesin), and how larger scale structures and functions within the cell e (e.g. , cytoskeletal dynamics,the cell division cycle, condensates) emerge from collective biophysical activity. Today the full complexity of those components is increasingly accessible using tools ranging from live-cell super-resolution microscopy to desktop genomic sequencing and single cell and image-based spatial transcriptomics, creating new opportunities for dissecting life’s fundamental principles across the biosphere. The high dimensional and multimodal data enabled by these new technologies, combined with computational power of AI/ML, is ushering in the next era of discoveries through “Cell Biophysics at Scale” (“Physiology 3.0”)
What to expect: The Physiology Course is designed to bring together people of many different disciplines (biology, physics, computation) to spark discovery. The emphasizes becoming comfortable with taking risks in teams, stimulating experimental creativity and applying interdisciplinary approaches to fundamental biological problems. After first gaining exposure to foundational concepts and skills, including building custom microscopes, purifying proteins, and developing custom AI/ML analysis for interrogating high-dimensional datasets, participants engage with a series of two-week research rotations using state-of-the art laboratory and computational techniques in a highly collaborative setting. The rotation projects are not “canned” lab demonstrations, but are instead active research problems brought by the course faculty from their home labs, with directions refined and defined in close collaboration with students, to tackle the biggest questions at the forefront of the field. Because the rotations focus on unanswered questions using emerging technologies, there is no “right answer”, and course participants are encouraged to actively define questions, innovate in the development of novel technologies, and boldly pursue field-defining discoveries. Participants of the course emerge as multilingual “integrators”, empowered to fearlessly pursue interdisciplinary collaboration.
Recent projects include: exploring how biomolecular condensates impact gene expression, characterizing Stentor regeneration after single-cell surgery, analyzing how macrophages and T cells make decisions about what targets to engage, examining RNA editing in squid and fungi, exploring how light activates multicellular contractility in animal-like protists, and discovering that viral proteins hijack the host actin cytoskeleton to trigger cell-cell fusion.
Daily schedule: Each morning begins at 9AM with an invited speaker talking about their field and their own cutting-edge research, followed by a student-only discussion with the speaker. Students then go to lab to plan experiments for the day with the course faculty and teaching assistants. During dinner, there’s typically time for students to go to the beach, exercise, socialize, practice for the annual softball game, or do laundry; we also have a few afternoon field trips, like collecting organisms from local waters, or a boat trip on MBL’s research vessel, Gemma. Afternoons and after-dinner are dedicated to data collection and analysis, with ample guidance from faculty and teaching assistants. Social hour is often punctuated by karaoke or time spent brainstorming around the whiteboard. The microscopes are typically humming late into the night. It’s a fun and energizing environment.
Join us! Graduate students, post-docs, and others with equivalent levels of experience are encouraged to apply. The typical class includes scientists with backgrounds in everything from the biological sciences to engineering, physics, and data science. Admission to MBL courses is “need-blind”—we will do everything we can to find funding for you if you’re accepted to the course! Please apply!