All biological phenomena are in a sense physical - every cell within our body divides, moves, transports cargo, and communicates with its environment. This simple perspective allows Dr. Raghuveer Parthasarathy at the University of Oregon to merge his studies of biology and physics to explore how life works. He is currently working to develop a physical, quantitative understanding of the principles underlying the behavior of various biomaterials and multicellular systems, with a particular focus on the diverse ecosystem of microbes that lives in all of our digestive tracts. In other words: how do the physical characteristics of biological systems impact their function? Are there general laws that describe phenomena like the growth of bacterial colonies, migrations of cells, and interactions between species that can allow us to make sense of biological complexity?

He and his team develop experiments that explore phenomena like the colonization of the gut by microbes and the mechanics of cellular membranes in order to illuminate general principles governing how these complex systems function.

• Microscopy Methods: Dr. Parthasarathy and his team develop new optical microscopy and image analysis methods to directly visualize structure and dynamics and translate them into biophysical insights. They measure, for example, the growth rates with which microbial species colonize the gut and how different species compete and spatially segregate, establishing niches that determine the structure of the microbial community. They also can create predictive models to see how they function and respond to perturbations like antibiotics.

• Microbiota: We have roughly 10x as many bacterial cells in our body as human cells. Most reside in our gut. They play an important role in how we function, and are involved in tasks as diverse as immune response and digestion. Microbial composition also influences such diseases as obesity, diabetes, and inflammatory bowel disease. Dr. Parthasarathy is looking at this complex and largely mysterious ecosystem that impacts the health and development of its host. Their work on the animal associated microbiota, using zebrafish as a model system, started a few years ago. They are at a transition point now between developing methods and applying them in zebrafish, a model vertebrate animal that shares many physiological similarities to humans, to explain the population dynamics of systems of gut microbes. They expect that the next few years will be particularly important, to demonstrate meaningful insights from this model system.

• Lipid Membranes: Lipid membranes make up the boundaries of cells and organelles, and their flexibility and fluidity are crucial physical determinants of their function. Dr. Parthasarathy's work on lipid membranes focuses on measuring the mechanical properties of membranes - their stiffness, bendability, and fluidity - by visualizing and perturbing their microscopic motions. They are characterizing these properties and seeing how proteins change those mechanical properties and interactions. Knowing how the mechanics and function of lipid membranes will help scientists understand how they relate to disease.

We live in an era in which new technologies readily deliver lists of biological components (genes, proteins, species of bacteria, etc.). Illuminating the mechanisms that connect these components to biological functions, or with aberrations such as diseases, is far more challenging. Such a mechanistic understanding is necessary if we are to rationally design new approaches to the treatment and prevention of disease, especially for very complex systems like the gut microbiota. (By analogy we would not approach aircraft engineering with just a list of parts, but rather with an understanding of how the interactions among the parts generate functions like thrust and lift.) Dr. Parthasarathy's research aims to provide mechanistic insights into a range of important systems. His team is determining, for example, the cooperative or competitive interactions between species of gut microbes, and the principles that underlie the usurpation of one species by another, which can help us understand the question of how to restructure the human gut microbiome.