In order for the cell to function properly, proteins must be robust to both changes in their environment and errors made during their synthesis. At the same time, proteins also need to be able to evolve novel functions to survive on long evolutionary timescales. The very same processes, i.e. genetic and phenotypic mutations, generate the diversity that leads to functional innovations and broken proteins, ultimately resulting in novel organisms, diseases and in some cases extinction.

In short, proteins exhibit evolutionary plasticity. But how do proteins remain robust and facilitate innovations at the same time? How can we distinguish variations, genetic and phenotypic, that are good or bad?

In my previous research I explored genetic variations, with particular focus on epistasis between mutations. In my new lab, we focus on phenotypic variations that are orders of magnitude more frequent than genotypic mutations. These variations are generated by the stochastic noise inherent to biological systems, such as transcriptional errors, ribosomal slippage, conformational flexibility and noisy expression. 

We aim to define and quantify the phenotypic plasticity of a protein, and to identify the compensatory mechanisms that buffer otherwise deleterious mutations. We wish to reveal the evolutionary potential of latent phenotypes to create novel functions and to influence gene-disease associations.

We mainly perform computational experiments using the vast amount of experimental data available (genome sequencing, RNA-Seq, mass-spectrometry proteomics), but we also test our hypotheses experimentally, generate our own data, and work closely with experimental collaborators and clinicians.

One gene – many proteins. Proteins are plastic molecules that can be described as ensembles of sequences, alternative structures with promiscuous functions, and ensembles of protein levels. All of these factors contribute to a variety of phenotypes. The phenotypic plasticity is due to stochastic noise inherent to biological systems, such as transcriptional error, ribosomal slippage, conformational flexibility and noisy expression.