Research

Cellular Signaling: Information Theory, Bacterial Chemotaxis, and GPCRs

How do cells regulate their behavior based on complex environmental signals? This question arises in a wide range of scenarios, from bacterial chemotaxis to physiological responses in multicellular organisms. Receptors play a crucial role in detecting these signals, which are transmitted via the activation of intracellular messenger proteins that in turn initiate appropriate cellular responses. Our research focuses on signaling as a many-body nonequilibrium process: how do collections of interacting receptors, coupled to nonequilibrium chemical reaction networks, allow cells to effectively propagate information?

Recent experiments, combined with our theoretical work, have demonstrated a new paradigm for our understanding of cellular signaling, highlighting the importance of nonequilibrium driving and cooperative interactions. We have developed nonequilibrium allosteric and nonequilibrium lattice models of the chemosensory array in E. coli that have demonstrated the key role of energy dissipation in enhancing response speed, sensitivity and robustness as well as the adaptive range of chemosensory signaling.

AlostericModel LatticeModel

Ongoing research in the group aims to develop increasingly detailed nonequilibrium statistical mechanics models of the bacterial chemosensory array to study structure-function relationships, signaling heterogeneity, and the microscopic mechanisms underlying adaptation. We are also starting to apply a similar modeling approach to study oligomerization and signaling responses of G-protein coupled receptors (GPCRs), in collaboration with the Gradinaru lab at the University of Toronto.

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Phase Transitions and Bifurcations

Many-body systems exhibit emergent phenomena: collections of spins, oscillators, or switches can organize into macroscopic collective phases: e.g. ordered vs disordered, synchronized vs desynchronized. Statistical physics and renormalization group theory predict that transitions between these phases exhibit universal scaling laws that are independent of microscopic details. We have developed techniques, built on a normal form theory for RG flows, to extend scaling theories beyond the critical region, enabling quantitative theories for thermodynamic properties over the entire phase diagram.

In a parallel line of research, we have leveraged normal forms to demonstrate that bifurcations serve as an organizing principle underlying soft robotics design. We developed a framework for tuning the dynamics of a magneto-elastic robot toward a high-order bifurcation, which allowed us to design transitions between multiple configurational states with only a few control parameters. This remains an active area of research, we are investigating the design of multi-state landscapes using many identical subunits, in collaboration with the Griniasty group at Tel Aviv University.

Bacterial Chemotaxis Bacterial Chemotaxis

Another current research focus is nonequilibrium many-body systems: characterizing their phase transitions, scaling laws, and the behavior of dissipation rates near phase boundaries. We aim to understand how nonequilibrium driving enables new collective phases and response properties that are not possible in equilibrium systems that satisfy the fluctuation-dissipation theorem. Our work both addresses these questions using both classical approaches and through the development of novel analytical and computational techniques.

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First-Passage Problems and Birth-Death Processes

A broad range of biological and soft matter systems, from chemical reactions and gene expression to ecological, evolutionary, and epidemiological population dynamics, can be described by stochastic birth-death processes. Furthermore, many such systems have threshold or absorbing states, where the dynamics change dramatically or even halt entirely; hence the first-passage time to these states is central to understanding these systems. We have studied universal properties of first-passage processes: do common distributions or scaling laws arise based on generic features of the underlying dynamics? We have also used first-passage techniques to understand applications such as fixation in evolutionary dynamics and clogging in granular flows. Current research focuses on both advancing our theoretical understanding: characterizing recurrence probabilities and quasi-birth-death processes, and on biological applications: modeling stochasticity, correlations, and extrinsic heterogeneity in gene expression.

UniversalDistributions GranularClogging

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Molecular Biophysics

Outside of the above research themes, we have a range of ongoing and completed projects utilizing nonequilibrium statistical physics to study phenomena in molecular biophysics, including the stepping dynamics of molecular motors, the assembly of bacterial flagella, and chromosomal segregation during cell division.

MolecularMotors FlagellaGrowth

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  • M. Halte, P.F. Popp, D. Hathcock*, J. Severn*, S. Fischer, C. Goosmann, A. Ducret, E. Charpentier, Y. Tu, E. Lauga, M. Erhardt, and T.T. Renault, "Bacterial motility depends on a critical flagellum length and energy-optimised assembly," Proc. Natl. Acad. Sci. 122, e2413488122 (2025). [PDF] [SI]
  • D. Hathcock, R. Tehver, M. Hinczewski, and D. Thirumalai, "Myosin V executes steps of variable length via structurally constrained diffusion," eLife 9, e51569 (2020). [PDF] [SI]