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Gene Function and Evolution

Group leader:  Gian Gaetano Tartaglia

 

One of the essential characteristics of living systems is the ability of their molecular components to self-assemble into functional structures. Equally important, however, is the way in which the processes leading to this organization are balanced within the cellular environment through the mechanism of homeostasis. Our research focuses on gene and proteins, since these are the molecules that enable, regulate and control all the chemical processes on which life depends. In order to function the large majority of RNAs and proteins need to fold into a specific three-dimensional structure. The wide variety of highly specific structures that results from protein folding, and which serves to bring functional groups into close proximity, has enabled living systems to develop astonishing diversity and selectivity in their underlying chemical processes by using a common set of just twenty building blocks, the amino acids.

Most of my research activity focuses on the understanding of regulation of gene expression and on the prediction of the mechanisms of protein folding and aggregation through a combination of in vivo, in vitro and in silico studies.

We have recently observed a remarkable anti-correlation between the expression levels of human genes in vivo and the aggregation rates of the corresponding proteins measured in vitro. A simple principle lies behind this link that arises from an evolutionary pressure acting to decrease the risk of aggregation in highly crowded cellular compartments. La raison d’être for this evolutionary pressure is that failure of proteins to fold correctly can give rise to cellular malfunctions and diseases. It is important to stress that the ability to form aggregates is not only restricted to proteins whose deposition is associated with specific diseases, but represents a generic property of polypeptide chains. In fact, the transition of normally soluble proteins to insoluble aggregates does not only imply a loss of biological activity, but results in production of species that are inherently toxic to cells, even when they are not associated with any known diseases.

I am currently investigating the conditions under which specific cellular pathways become aberrant and give rise to pathologies. This project, that we call pathosome, involves the in silico prediction of changes in protein-protein and protein-gene interactions that impair cell viability and will have an experimental validation in vivo.

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