Life is a collection of processes on many different scales: miliseconds to centuries, nanometers to kilometers. As our capacity for information processing is finite we naturally zoom in and out between these scales to build a mental model of the world: We pick up a few key elements and coarse-grain the details. In my research I use a similar approach of a coarse-grained modeling to capture complex biological phenomena.
While the main focus of our research is on common logic of stress response systems, we are gradually expanding into the field of stem cell differentiation (in collaboration with our collegues at Stem Phys).
Stem cell differentiation
How do cells communicate and coordinate their fates to arrive at right proportions of differentiated cell types? How flexible/reversible are the transitions between differentiation states? Are there common principles (despite different set of proteins) at different differentiation stages and across organs? We address these questions in collaboration with Joshua Brickmann (ES cells, arly blastocyst) and Anne Grapine Botton (pancreas) labs theoretically by in-silico models and experimentally by quantitative single-cell imaging and rna and protein profiling.
We strive to quantitatively understand the logic behind stress responses and how it unfolds itself in time and across cells in the tissue. What mechanisms did cells and organisms evolve to deal with the insults that perturb their normal function (stresses)? What are the differences and similarities between the stress responses? (Both at the level of regulatory network and the dynamics of its components in single cells and on a cell-population level). With this knowledge and with the help of mathematical modeling the hope is to outline the "core circuits" that govern a given process. For this approach we employ a variety of theoretical tools complemented with experimental techniques (e.g. time-lapse of fluorescently tagged proteins in single cells) whenever possible.
Part of our current activity is on the stress response processes that are directly involved in diseases:
- Unfolded Protein Response (Diabetes, with Feroz Papa, UCSF);
- DNA damage and response to genotoxic stresses, telomeres dynamics (Aging, Cancer)
- Osmotic stress and p53 dynamics in single cells (with Else Kai Hoffman, KU)
- Dynamics of NF-kB meditated inflammatory response in tissue (Inflammation);
- Dual roles of IL-1beta in pancreatic islets (with Thomas Mandrup-Poulsen, KU, Panum)
- Spatio-temporal regulation in monolayer cell culture (with Savas Tay, ETH, Basel
- Epigenetic landscapes in Pombi (with Genvieve Thon, KU)
- GPCR regulation in yeast S. Sacc. (with Sergio Pejsajovich, Un. Toronto)
- Bacterial heat shock (with Steen Pedersen, KU)
- Asymmetric damage segregation in E.coli (with Andrej Kosmrlj, Princeton)
We use agent based modeling to capture the possible mechanisms of species coexistence, epidemics and concurrent immunity spread of multiple competing diseases, or to explore the role of bacterial immunity (CRISPR) in phage-bacteria ecosystem.
Physics of Molecular Diseases
Numerical Methods in Physics