Microorganisms are in continuous interaction with their environment as well as with each other. These interactions introduce a wide range of fluctuations that can influence cell growth and protein expression dynamics. In addition, intracellular biochemical processes are subject to significant molecular noise. Nevertheless, microorganisms are able to maintain cellular homeostasis to promote stability. The control mechanism underlying cellular homeostasis has yet to be discovered despite extensive efforts. To address this problem, the PI has recently examined cell size dynamics in long lineages of bacteria measured at the single-cell level. The results revealed a feedback mechanism that acts to maintain cell size by adjusting the cell's growth rate after every division event to offset deviation from the "desired" size generated by the division. However, despite this fast response to size deviation, cell size exhibits long term memory that lasts for multiple generations. This memory is clearly manifested in the epigenetic inheritance patterns measured by the PI using recently developed experimental techniques. The proposed study aims to further investigate the cell size homeostasis and reveal its underlying control mechanism. It also aims to quantitatively measure the non-genetic inheritance patterns of the different cellular traits and determine their effect on the cell size variation over time. The study will make use of new experimental techniques coupled with a mathematical framework to model the results and provide testable predictions to guide future experiments. The project will integrate research in the interdisciplinary field of biological physics with education in order to develop new instructional material for undergraduate and high school students. This is crucial for today's science education because of the increasing need for quantitative understanding of biological systems in research and industry. The PI's plan is to: (i) Include high school teachers and students in research projects in the PI's laboratory and develop instructional material based on their work to be distributed to high schools in the area. Students from under-represented minority groups are particularly encouraged to participate in this initiative, and (ii) Develop biophysics experiments for students' undergraduate laboratories. The program will expand the science curricula of the undergraduate program and of high schools in the area to include material in the interdisciplinary field of biophysics. This will increase the interest among high school students in the field and encourage them to pursue higher education in science. It will also provide undergraduate students with more career and education opportunities, which can attract more students to the physics department at the University of Pittsburgh.
Cellular homeostasis is a fundamental process for all self-replicating organisms. It is what ensures reliable progression of living cells. Therefore, it is of paramount importance to understand its control mechanism. In addition, non-genetic phenotypic inheritance, which works to maintain cellular properties along generations, plays an important role in many biological phenomena. The change of cellular properties over time can often help the cell survive a changing environment. In other instances it can be detrimental such as in the case of the growth of cancer metastasis. Thus, the ability to measure inheritance patterns and characterize them quantitatively will allow us in the future to predict cell fate and modify it if needed. The research proposed will deliver new experimental data that challenge existing theories. It will also provide a comprehensive description of how the long-term inheritance and the fast intracellular processes integrate to achieve stable cellular traits, and at the same time generate a wide range of phenotypic variability among members of the population.
This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.
