What determines growth rate in bacteria and gives rise to the enormous variation between environments?
This has led us to study tradeoffs between growth and adaptability / resistance / survival and try to uncover underlying mechanisms linking these competing objectives.
Tradeoff between growth and adaptability quantified (Basan et al. Nature 2020).
What are the benefits and costs of different metabolic strategies?
For instance, why do cell use overflow metabolism (also known as the Warburg effect in cancer cells) instead of respiration in some conditions, but not in others? How do these metabolic programs affect growth rates of cells in culture and but also in a tissues, for example a small tumor?
Fermentation enables faster growth by having a leaner enzymatic machinery (Basan et al. Nature 2015).
How do cells achieve homeostasis of cell size and cellular composition? When does a cell divide? How are growth of protein, RNA, DNA, lipids production and water content coordinated?
We are interested in these questions both for microbes and for cells in tissues.
Cells can be inflated by expression of large quantities of harmless protein (Basan et al. MSB 2015).
Quantification of cell size by electron microscopy together with Harvard CNS.
How do cells in a tissue interact to achieve homeostasis?
We are particularly interested in what underlies the phenomenon of cell competition to study how homeostasis breaks down during early tumor growth, as well as the role of mechanics in this process. What determines growth rates of tumorous clones in a tissue context?
GFP expressing mutant clones are eliminated wiith increasing induction (right to left) in Drosophila tissues.
Our approach relies on the close coordination and mutual feedback between experimental and theoretical efforts. We calibrate, test and refine our models in multiple rounds. Typically, we combine careful characterization of physiology, genetic perturbations, omics technology and theoretical models.