Viral life cycle

Structural biology of viral membrane fusion

The aim of my project is to shed light on proteins interactions occurring between viruses and their host cells. Viruses use host cell resources to carry through their life cycle, but infection triggers host cell antiviral defense mechanisms that in turn drive viral adaptation. Thus it is crucial to understand not only the biology of the virus but also the biology of the host and the different cell pathways hijacked by the virus. This project will initially focus on unravelling the mechanism of viral membrane fusion.

Structural biology of TIP30 complexes

The lack of effective therapies against many cancers and against several viral infections have highlighted the need to firstly understand the mechanisms involved in tumourgenesis and viral activity, and secondly to design drugs targeting particular proteins. In order to develop specific and efficient antiviral and antitumour drugs, a combination of biology, biochemistry, chemistry and structural biology is essential. The work presented here is aimed at defining the biological mechanisms and structural features of TIP30 and its protein partners, involved in cancers, Human Immunodeficiency Virus (HIV) and multiple sclerosis, and thus, providing the ground-work to help in the design of new molecules modulating TIP30 functions.

Native phasing

Single-wavelength anomalous dispersion of S atoms (S-SAD) is an elegant phasing method to determine crystal structures that does not require heavy-atom incorporation or selenomethionine derivatization. Nevertheless, this technique has been limited by the paucity of the signal at the usual X-ray wavelengths, requiring very accurate measurement of the anomalous differences. I23 has been designed to provide an optimized environment for difficult S-SAD experiments, by increasing the anomalous signal with minimal noise.