The previous posts lead me to introduce my Fellowship project: I am exploring the role of some novel G-Protein Coupled Receptor (GPCR) signalling pathways (some particularly structured antennae whose signals and way of signalling is still to be clarified). I’m particularly interested in the physiology of the islets of Langerhans, which are clusters of cells in the pancreas that produce the hormone insulin. Where have you heard of insulin before? Of course, it’s that protein that is needed to regulate blood sugar levels and when there isn’t enough of it or it doesn’t work properly, Diabetes develops. Diabetes is a huge global problem, and around 400 million people worldwide currently have this condition.
My project aims to provide the molecular basis for the development of new medical tools based on the GPCR activity to prevent, treat and eventually cure Diabetes.
So, going back to our image of a cell as a spherical house, a GPCR is a particular antenna that crosses the dome many times. Yes…crazy uh! And if I ever mention a transmembrane territory (TM) in the future posts, you know I am referring to this dome-crossing feature.
This dome-crossing structure consists of 3 parts called the N-terminus (sticking out of the dome) and the C-terminus (sticking out inside the dome) and the transmembrane territories.
Proteins are made from small building blocks called amino acids that link into long chains. We refer to the ends of these chains as N and C termini to orientate the protein. So N and C work for biologists as North and South or East and West do for sailors (or tourists in the USA!)
If you remember the antennae structure, the N-terminal domain is capable to detect the signal (known to biologists as a ‘ligand’) on the outside of the dome, thus it is defined as the Ligand-Binding Domain, while the C-terminal domain is capable to initiate a series of event on the internal side of the dome that results in a specific effect within the cytoplasm.
So imagine that there is a currency in the cytosol. Signals are received by the N terminus and conveyed to the C terminus. The C terminus then can recruit effectors by spending its currency – this GPCR currency is called GTP. When there is no signal, the C terminus does nothing and doesn’t spend GTP and the receptor is at rest. The equivalent of the purse strings tightening.
So my aim is to consider how the cells respond to the money expenses through GPCRs, specifically those belonging to short chain fatty acids families which we think may be involved in insulin secretion mechanisms.
To pursuit these aims I have been appointed as Research Fellow at the division of Diabetes& Nutritional Sciences of King’s College London, as result of being entitled with a Marie Curie Intra-European Fellowship.