Order-parameter based feedback motifs in signal integration and lipid homeostasis

• Applicant: Dr. Isabella Graf
• Subject Area: Statistical Physics, Nonlinear Dynamics, Complex Systems, Soft and Fluid Matter, Biological Physics
• Term: from 2021 to 2024
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 494077061

Biological systems must sense and respond to faint external signals. Detecting these weak signals often requires integrating information from many individually noisy molecular sensors. But how could cells extract and distill this dispersed information to make coherent decisions? One appealing mechanism is to embed the sensors into a broader thermodynamic or dynamical system which naturally amplifies small changes in external signals into large cooperative changes in system behavior. However, such responses generally require control parameters to be tuned close to special points in parameter space, so-called critical or bifurcation points, which mark transitions between regions with qualitatively different collective behavior. In principle, very precise tuning of the control parameters could occur for example by evolution, but this does not seem plausible for biological systems that are subject to fluctuations and changing environmental conditions. Alternatively, suitable feedback schemes may return these systems to their sensitive, critical regions. In the proposed project, we will examine one class of feedback motifs where the system – instead of regulating the control parameter to a certain, fixed value – measures an intrinsically collective system property, an order parameter, and responds to it by then feeding back onto the system’s control parameter. We ask whether schemes of this class naturally tune the underlying system close to a critical or bifurcation point. To address this question, we will employ methods from theoretical (bio)physics and pursue a two-fold approach. First, we will investigate conceptual models for two specific sensing schemes (bacterial chemosensing and the hearing mechanism of the inner ear) as well as a system for which proximity to a thermodynamic critical point has been demonstrated experimentally (the Eukaryotic plasma membrane). Using the insights gained from these qualitatively different systems, we will then develop a general information-theoretic perspective to more broadly understand the role of our proposed feedback motif and its dependence on characteristics of the transition like the number of control parameters that need tuning or the underlying universality class. Overall, our analysis will contribute to the identification of important principles of biological sensing and robust tuning. For instance, there has been enormous progress in understanding lipid homeostasis at the molecular level, and a fascinating but mysterious finding of active tuning of membrane composition close to a critical point, but no broader framework to attach either of these topics to. We hope that through close collaboration with the experimental laboratory of Sarah Veatch (University of Michigan), a leading expert in membrane phase behavior, our work might shed light on this open question. Finally, our project might provide useful guidelines for synthetic biology and the robust design of artificial high-sensitivity sensors.

• DFG Programme: WBP Fellowship
• International Connection: USA
• Host: Professor Dr. Benjamin Machta