Focus

Biological modeling; intracellular networks; molecular biophysics

Research

Intracellular networks in bacteria

Bacteria are constantly sensing their environments and adjusting their behavior accordingly. Signaling occurs through networks of proteins and nucleic acids, culminating in changes of gene expression and so changes in the proteome of the cell. We are focused on the architecture of these intracellular networks. What is the relation between network architecture and function? For example, can we understand the selection of architectures in terms of general information-processing concepts such as signal to noise, memory, and adaptation? Even in a single bacterium such as E. coli, there are hundreds of coexisting networks. Our belief is that a deep study of a small number of "model" networks will yield general tools to analyze information processing by cell. It is important to choose these model networks carefully. The network components should be well-characterized and the physiological function of the network should be known and subject to quantitative measurement. Probes of the internal dynamics of the network such as fluorescence resonance energy transfer (FRET) or direct imaging of dynamic spatial structure, will be critical in developing and testing quantitative models. It is also important to choose networks which complement each other well, spanning a broad range of architectures and functions.  Over the years, the group has studied (i) quorum sensing, in which the cell slowly integrates signals from its neighbors to commit to a developmental decision such as invasion of a host, (ii) chemotaxis, which requires adaptation and rapid response to changing chemical concentrations, (iii) cell-division networks, where accuracy and checkpoints are essential, and (iv) metabolic networks which tie together diverse inputs to maintain homeostasis. These studies have greatly benefited from our long-term collaborations with the Bassler, Gitai, and Rabinowitz labs at Princeton.

Microbial communities

Biofilms, surface-attached communities of bacteria encased in an extracellular matrix, are a major mode of bacterial life. We collaborate with the Bassler and Stone labs at Princeton to study many aspects of biofilms, from their formation and maturation to their eventual disassembly, mostly using Vibrio cholerae as a model organism. The detailed experimental observations on biofilms call for biophysical modeling, and to this end we have developed both agent-based and a continuum models that capture the distinct stages of the biofilm lifecycle. We also collaborate with the Shaevitz lab in studies of activity-driven pattern formation by the bacterium Myxococcus xanthus, which aggregates and forms fruiting bodies in response to starvation. Finally, we are broadly interested in microbial diversity – why are there so many different species in essentially ever microbiota? We collaborate with the Donia lab to better understand the ecology of microbes in nature.

Intracellular phase separation

Biologists have recently come to appreciate that eukaryotic cells are home to a multiplicity of non-membrane bound compartments, many of which form and dissolve as needed for the cell to function. The data are accumulating that these dynamical biomolecular condensates enable many central cellular functions – from ribosome assembly, to DNA repair, to cell-fate determination – and understanding them will be the key to unlocking some of the most recalcitrant problems in cell biology. It seems clear that these compartments represent a type of separated phase, but there are many open questions concerning their formation, how specific biological components are included or excluded, and how these structures influence physiological and biochemical processes. In these studies, we collaborate closely with the Brangwynne and Jonikas labs at Princeton.

Biography

Ned Wingreen is the Howard A. Prior Professor of the Life Sciences at Princeton University. He is a member of the Department of Molecular Biology and of the Lewis-Sigler Institute for Integrative Genomics, where he is Director of Graduate Studies of the QCB Graduate Program. He is also Associate Director of the Princeton Center for Theoretical Science, and associated faculty in the Department of Physics. Ned received his Ph.D. in theoretical condensed matter physics from Cornell University in 1989. He did his postdoc in mesoscopic physics at MIT before moving, in 1991, to the NEC Research Institute in Princeton. At NEC, he continued to work in mesoscopic physics, but also started research in biophysics which grew into a general interest in problems at the interface of physics and biology. Ned joined Princeton University in 2004. Ned's current research focuses on modeling intracellular networks in bacteria and other microorganisms, as well as studies of microbial communities, and intracellular phase separation. He is a fellow of the American Physical Society and the American Association for the Advancement of Science.

Honors & Awards