Abstract:

The crowded cell interior relies on many quality control mechanisms to ensure the correct protein machinery is present in the right places at the right times. I will present two projects currently underway in our lab that unite within this theme. We use a range of biophysics techniques, including NMR, X-ray crystallography, cryo-electron microscopy, SAXS, EPR, native mass-spectrometry, and more, to study structure, function and interactions of proteins involved in these processes.

Metabolic Shutdown in Sporulation

When certain bacteria find themselves in unfavourable growth conditions such as nutrient deprivation, they make a carefully choreographed lifestyle switch to a hardy dormant form called a spore which will survive harsh conditions and revive when the time is ripe. One aspect of sporulation is metabolic shutdown of the developing spore and I will present some work we have been doing to understand this process in Bacillus subtilis.

Triage of Mislocalised Proteins

In mammalian cells, a co-chaperone called SGTA (small, glutamine-rich, tetratricopeptide repeat protein alpha) plays a critical role in sorting hydrophobic parts of proteins that have become aberrantly exposed to the aqueous cytoplasm. These are thought to meet with one of three fates: targeting to a membrane, refolding by chaperones or degradation by the ubiquitin proteasome pathway. SGTA also stabilises steroid hormone receptors before they are activated for nuclear entry by their hormone ligands. I will show our recent findings on understanding this complex tweezer-like protein using a combination of methods.