HHMI adds new research focus on 4D cellular physiology

4D image 1

The Howard Hughes Medical Institute (HHMI) is adding a new research direction, 4D cellular physiology, to its current portfolio of research interests, which includes mechanistic cognitive neuroscience. The ASCB Newsletter posed a few questions to Ron Vale, the Vice President and Executive Director of HHMI’s Janelia Research Campus, and Jennifer Lippincott-Schwartz, a senior group leader also at Janelia, about this new direction and how it will impact the cell biology community.

How do you define 4D cellular physiology?

JLS: I would say it is the structure and function of cells in their native tissue environment, moving our study of cell biology out of a context of tissue culture and into an organism. Cells are part of communities and we have the tools that allow us to start interrogating this environment that we have not been studying so effectively in the past in tissues and in whole organisms.

RV: Physiology has historically taken a bigger system-wide view of the body, trying to understand how organs work, how they monitor external and internal information, how all these organ activities are integrated, and to bridge these worlds that span from the cell at the microscopic level. Combining cell biology and physiology represents a grand challenge for the future and an exciting challenge for cell biologists who are trying to understand these systems across scales. It’s going to require a really interdisciplinary effort to tackle these big problems.

Why is this particular focus important right now?

RV: The tide is ready to turn back to where the field started, which is taking cell biology back to these complex environments of how tissues work. I think we’re armed now with an understanding of how cells work. That reductionist approach (taken by cell biologists) built up a suite of tools and fundamental understanding. It’s much harder to do these studies in living tissues or engineered tissues, but I think it represents a great challenge for a whole research community right now and that’s why we are excited about it. Even late in our careers, Jennifer and I are personally interested in taking on this challenge, and we hope that lots of young people will see this as their future.

The villi of adult mouse jejunum projecting into the lumen of the intestine (Melinda Engevik, Baylor College of Medicine)

Why is the Janelia Research Campus uniquely qualified to tackle this research focus?

JLS: Janelia has a really interesting structural organization where there are small research groups that are combining with project teams and other sort of efforts that allow for innovative exploration of not only true development but also computational advances. The hope is that Janelia can be like a test bed for this effort. We have some major technology that we think can play a big role—among them whole volumetric electron microscopy where for the first time you can section through entire cells at very small volumetric scale but you can also section through whole tissue. Using machine algorithms you can then reconstruct subcellular organization as well as the distribution of cells. That will allow us to begin to clarify cell identifies and subcellular structures. It’s a huge effort and Janelia has the tools to make this happen.

The goal is to try to engage the rest of the world’s community in trying to understand what is being seen in these new datasets. There are some spectacular live-cell imaging approaches that are being spearheaded at Janelia that we hope can be incorporated in this effort. We think that Janelia has some advanced tools that are perfectly suited to this particular area and thus can be used as a way to jump off into it. Janelia also has a large visitor program and an open microscopy core and advanced imaging center that embraces the idea that people come to Janelia do collaborative work. My sense is that Janelia is wonderfully situated to help spearhead this effort.

Workshops and Conferences

HHMI is hosting a series of free online workshops and conferences related to 4-D Cellular Physiology and featuring talks from experts as well as early career scientists, which can be found at www.janelia.org/you-janelia/conferences/conferences.

The full interview with Vale and Lippincott-Schwartz can be found on the Pathways Podcast at https://anchor.fm/ascb-pathwayspodcast/episodes/What-is-4D-Cellular-Physiology-with-Ron-Vale-and-Jennifer-Lippincott-Schwartz-eu40mn.

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Mary Spiro is ASCB's Science Writer and Social Media Manager.