Physical Biology Laboratory
Department of Physics and Astronomy - University of Pittsburgh
General:
Our research aims to understand the mechanisms of collective behavior and variability in bacterial cultures and their effect on the response of bacteria to changes in the environment. The continuous interaction between the environment and living organisms is one of the main effectors of evolution. There are many known strategies of responding to environmental changes, e.g. by changing the swimming pattern or the gene expression profile. And although many strategies are single-cell based, we often see cooperative behavior arising among members of the colony under certain conditions. By studying the changes in the behavior of bacteria as a function of their concentration, we are able to detect some of the collective mechanisms that govern the bacterial behavior and allow them to better endure environmental stress. Environmental changes that interest us are thermal and chemical. We utilize various optical microscopy techniques to observe the swimming pattern of bacteria under different conditions. As for the expression level of proteins, proteins of interest are labeled with fluorescent markers and the expression level is measured using fluorescence microscopy or flow cytometry.
Collective Dynamics: How do bacteria communicate and coordinate their behavior?
Cells in a population often communicate with each other to coordinate their behavior and motion. This can help them reach their targets faster and protect themselves from invasion by predators, or in the case of bacteria can even help them resist treatments with antibiotics. Bacteria communicate by secreting chemicals, which can influence the behavior of neighboring cells and/or attract them to create an aggregate of cells that can move together or colonize certain regions. Our research aims to understand the different mechanisms of cell-cell communication and more importantly, how this communication affects the behavior of the population. This can shed light on the benefits of cell-cell communication to the population's survival and help us understand how to manipulate it to our benefit.
Bacterial Thermotaxis: How do bacteria sense and respond to temperature changes?
We are studying how bacteria find and choose safe environments for their growth when they are subjected to changes in temperature. Our research aims to understand how bacteria navigate their way through an environment, where the temperature at different locations is different, by sensing the changes in temperature along their path. We also look how temperature changes the bacteria and their behavior along that journey. A better understanding of these questions may help us in the future develop artificial biological sensors. In addition, since bacteria can utilize temperature sensing to locate and infect host cells, a better understanding of bacterial thermotaxis can help us develop treatments to prevent bacterial infections.
Fluctuations in Protein Expression in Bacteria: What determines cell-to-cell variability?
The protein content of biological cells is a major determinant of their behavior and function. Yet, the copy number of any specific protein
varies widely among individuals in a cell population, even in genetically identical cells grown under uniform conditions. In this research, we aim to understand the sources of variability in protein expression among genetically identical cells, and determine its benefits and disadvantages to the population. This is a very important question, since variability plays an important role in diverse biological phenomena including the response of the immune system to infections, the growth of cancer metastasis, the formation of tissues during development, virus infections, and microbial behavior.
Epigenetic Inheritance Dynamics: What determines cellular memory and restricts variability?
Heterogeneity in physical and functional characteristics of cells, such as cell size, protein content, or growth rate, proliferates within an isogenic population due to stochasticity in intracellular biochemical processes and in the distribution of resources during divisions. On the other hand, it is limited in part by the inheritance of cellular components between consecutive generations. In this part of the research we are interested in quantifying the inheritance dynamics and its restriction of cellular heterogeneity. To this end, we have developed an experimental method for measuring proliferation of heterogeneity in bacterial cell characteristics, based on measuring how two sister cells become different from each other over time. This new method allows us to measure the inheritance dynamics of the different cellular properties, and extract the cellular memory for each property quantitatively. We intend to use this technique to reveal mechanisms of non-genetic inheritance and their memory in bacteria in order to better understand how cells control their properties and heterogeneity within isogenic cell populations.