TL Liu et al., 2018
Credit: TL Liu et al., 2018

Physiology encompasses the functions carried out by different organs and tissues in the body that allow an organism to eat, breathe, reproduce, and continuously adapt to changing conditions to ensure survival. Fundamentally, these functions are produced through the collective actions of cells, thousands and trillions of which comprise a simple worm and a human body, respectively. We still have a poor understanding of how cellular processes − which cell biologists seek to explain at the level of molecules, organelles, and cell-cell interactions − give rise to the systems-level phenomena that are described by physiologists.

4D Cellular Physiology aims to fundamentally alter this landscape by establishing strong technical, biological, and conceptual bridges that bring physiology within reach of mechanistic cell biology. We feel that this problem is now at a turning point with tools, existing or within reach, for measuring dynamics of heterogeneous cells within tissue environments and harnessing computation and theory to understand how communities of cells self-organize and communicate to create functional organs and organisms.

4D Cellular Physiology is a grand challenge, one that will excite current and future generations. Janelia certainly cannot do it alone, nor would we want to. The 4D Cellular Physiology workshops introduced us to wonderful colleagues around the world. We want to stay in touch, interact, and have 4DCP at Janelia aid your work, whether through in-person or virtual conferences, our visitor’s program, the Advanced Imaging Center, collaborations, tools that we develop, or data that we share. We are all part of one big network of science, and only through that network can we hope to understand the network of cells that make us who we are.

Learn more about Janelia’s scientific programs, support services and campus amenities on Janelia.org.

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The name 4D Cellular Physiology encompasses several elements of the challenge and the aspiriations of the research at Janelia.

  • 4D emphasizes both the need to study 3D multi-cellular systems, and not just 2D monocultures, and to study dynamics of cell behavior and communications over time, and not just snaphots.

  • Cellular emphasizes the units that comprise the organism; recent genomics indicate the cells of the body are much more heterogeneous than previously imagined and thus a realization of a need to make measurements of cells as individuals, and not just as averaged populations.

  • Physiology frames the macro-level systems phenomena and questions that need cellular and molecular explanations.

New tools are needed to drive 4D Cellular Physiology forward as a field.

  • Progress in 4D Cellular Physiology will require a suite of new tools for investigating and conceptualizing the connection between cell behavior and physiology. The core tool research areas of Janelia (Computation & Theory and Molecular Tools & Imaging) are well-suited to connect and bootstrap between the different length (nanometers to meters) and time scales (milliseconds to days) that connect the worlds of cell biology and physiology. Janelia is a special environment that supports tool builders, technology developers, and computer scientists who can push their talents and work in close collaboration with biology-focused tool users. We welcome new tool builders as well as biologists to join us at Janelia and propel the emerging field of 4D Cellular Physiology.

Tools at Janelia can help bridge scales
  • 4D Cellular Physiology synergizes well with our current research area, Mechanistic Cognitive Neuroscience. Just as 4DCP aspires to bridge the fields of cell biology and physiology, MCN aims to connect the fields of cognitive psychology to mechanistic cellular and systems neuroscience. Both programs have a shared goal of understanding how animals behave and coordinate their responses at different biological scales (i.e., molecules, cells, organs, and whole body) to promote survival under a broad range of conditions. Both use technologies to study cells in their native tissue environments. The peripheral nervous system, which links the body and the brain, also will likely comprise one element of the 4DCP program.

We aim to create a unique and interactive community at Janelia that can stimulate us individually and collectively to think about the overarching problem facing the field − understanding the general principles of how cells self-organize and how information flows across scales to create multicellular life.

  • 4D Cellular Physiology is a new research area that will comprise 15 laboratories, hired over the next few years, that will be internally funded for 15 years. In addition, we will hire new Group Leaders and Senior Group Leaders in the tool areas of Molecular Tools and Imaging and Computation & Theory whose work will be related to 4DCP. We will launch Project Teams that will tackle problems in 4DCP (see CellMap). Many of our current scientists also are interested in working on 4DCP (see Meet Our Scientists).

  • With a critical mass of current scientists and those who will come to join us, we will create a unique intellectual community of scientists who are dedicated to a mechanistic cellular-level understanding of physiological problems. Within this large undertaking, we plan to identify subareas of focus based upon scientific synergies that we see emerging from our pool of applicants, and are interested in hiring clusters of scientists who would be excited to work together.

  • The true scope of 4D Cellular Physiology will require decades of work from scientists around the world. We are exciting to make Janelia an engine that drives progress for the entire field and look forward to the many interactions and collaborations that we form over the coming years.

Janelia hosted a series of monthly workshops aimed at thinking about questions at this emerging interface. We discussed questions, such as how the liver knows to regrow after injury and how it knows when it has reached the right size and should stop growing. How do nerves sense the nutrients, motility, and microbiome of the gut, and how is this information carried to other organs and the brain? We also discussed the cellular ecosystem that governs the shape, functions, and behavior of an animal as simple as a worm, most of which remains poorly understood. We encourage you watch a few of our featured workshop talks (10 min each) to get a feel for the types of problems that could be addressed in a 4D Cellular Physiology research program. Visit the Janelia YouTube Channel for full recordings of all past workshops.