Felix Barber - How do cells robustly regulate their size? We have long known that cells couple their growth and the cell division cycle, resulting in constraints on the distribution of sizes seen across a whole population of cells. In budding yeast, this coupling occurs primarily in the first cell cycle of newborn daughter cells, with smaller daughters taking longer to pass through Start. However, the means by which cell size influences the decision to pass through Start remains unclear. We are addressing this question through single cell correlations and genetic perturbation experiments.
Miguel Costa Coelho - I am interested in how mutation rates evolve and how genetic instability changes under different selective pressures. To understand that I have used experimental evolution of diploid budding yeast cells, placed under selective pressure to inactivate growth suppressor genes sequentially, mimicking tumor growth suppressor inactivation during cancer progression. By doing this I have evolved high rates of point mutation, recombination and chromosome loss. After whole-genome sequencing and genetic reconstruction analysis I found that besides DNA repair pathways, other cellular processes change to cause genetic instability, and when I tested some of these new instability genes by deleting their corresponding homologs in human cells instability was largely conserved. Understanding how genetic instability evolves is important for cancer resistance to drug therapy, pathogen adaptation to antibiotics and in general to understand how changing mutation rates confers a selective advantage.
Marco Fumasoni - I’m broadly interested in genome evolution and how it’s intertwined with the molecular mechanisms that replicate and organize the chromosomes within the nucleus. I currently focus on two main projects: in the first I’m studying the evolvability of an essential system, the DNA replication machinery. In the second, I’m developing an experimental model of adaptive radiation to study the origins of novel features in biological evolution. In my research, I take advantage of budding yeast as a model of the eukaryotic genome and I use experimental evolution to observe selection acting on it. I then combine sequencing, cell, molecular and systems biology approaches to dissect the molecular events that allow genome adaptation to different conditions.
Andrea Giometto - Microbes often live in dense populations, such as colonies, tissues and biofilms. In these settings, proliferating cells exert mechanical forces on nearby ones, causing local rearrangements within the population and coupling the dynamics of cells over spatial distances much larger than a cell diameter. I study how these growth-induced mechanical forces affect microbial competition in growing yeast colonies and their implication for the spread of favorable mutations and the extinction of deleterious ones. By growing mixed colonies of two yeast strains with different fitnesses on solid agar plates, we found that growth-induced physical interactions reduce the power of natural selection in growing colonies (https://www.biorxiv.org/content/early/2018/05/29/332700). As a result, selective sweeps (i.e., increases in the frequency of a fitter strain at the frontier of growing colonies) are slowed down by physical interactions and less-fit strains survive for long times at the colony frontier. The prolonged survival of less-fit strains occurs via the formation of thin, persistent filaments that are pushed towards the exterior of the colony by nearby fitter cells. These filaments favor the maintenance of genetic diversity in mixed-strain colonies growing in environments in which the strains' relative growth rates vary with time. We use models inspired by overdamped hydrodynamics to investigate how the spatio-temporal dynamics of strains competition depend on the relative fitness of different strains and on the physical properties of yeast colonies.
The figure shows a mixed-strain colony grown in an environment that alternated between two temperatures at which the yellow and blue strain relative growth rates varied. At each temperature, the slower-growing strain survived as thin, persistent filaments that allowed it to recover at the colony frontier following changes in temperature.
More information on other research projects coming soon