Scheme: Dorothy Hodgkin Fellowship
Organisation: Birkbeck College, University of London
Dates: Oct 2014-Sep 2019
Summary: I am a Dorothy Hodgkin Research Fellow at the Institute of Structural and Molecular Biology at Birkbeck College, part of the University of London. My research targets fundamental questions in protein trafficking and secretion. In particular, I aim to understand how the collagen precursor (procollagen), a very elongated molecule, goes through the cellular secretory pathway, which typically deals with small cargoes.
It is important to understand the molecular mechanisms of procollagen secretion, as its dysregulation is a hallmark of a number of diseases of the extracellular matrix, from genetic disorders to fibrosis.
Proteins reach the extracellular environment as cargo transported into membrane vesicles formed by means of protein coats. COPII is the protein coat responsible for the exit of cargo proteins from the endoplasmic reticulum, and it functions by inducing formation of relatively small vesicles.
Some cargos, including procollagen, are too big to be transported in default COPII vesicles, and the components of the coat are thought to rearrange to form megacarriers. Procollagen-specific factors seem to promote this process although the mechanisms remain poorly defined.
A very powerful way to study the molecular mechanisms of megacarrier formation is the direct visualisation of COPII-coated vesicles reconstituted in vitro under controlled and regulated conditions. I use cutting edge techniques, in particular cryo-electron tomography and subtomogram averaging, to discern the architecture of the coat on budded membranes at sub-nanometer resolution.
Together with complementary functional approaches, such as immunofluorescence microscopy, my studies will help understand fundamental unresolved questions in the field of procollagen secretion, and will therefore have a potential long-term impact on the biomedical community.