Wait - you're doing ANOTHER three years of University?

My PhD is in Biophysics. Yeah, biophysics. I normally get the following response:

Starting only this week, I'm still finding my feet in the lab where I'm working, and I'm only beginning to scratch the surface of the mountains of literature which are pertinent to my (impenetrable)PhD title: 

G-protein regulation phosphoinositide 3-kinase conformation and dynamics in signal transduction, autophagy and cellular sorting.

Or to paraphrase:

Cancer. 

Because, eventually, everything you learn in biochemistry will, in some way, and at some time be made applicable to cancer.


In all seriousness though, this PhD is actually relevant to cancer. The main focus of my study are phosphoinositide 3-kinases (PI3 Kinases for short), which are pretty interesting little enzymes. Kinases are enzymes which phosphorylate - i.e. tag a phosphate group onto a target. The target of PI3 Kinases being a molecule of fat - called phosphatidylinositol - which is part of the cell membrane.


Phosphorylation is a big deal in biochemisty. It's how everything gets done. Attaching a phosphate group to an enzyme is the atomic equivalent to flicking a molecular switch (although not necessarily onto the "on" position). Phosphate groups consist only of a handful of atoms, but can radically change the workings of a entire enzyme -consisting of many thousands of atoms. These little phosphate achieve these enzymatic adjustments by altering the local electrostatic environment fairly drastically - causing a of modification to the shape and dynamics of protein, fundamentally responsible for any changes in activity. It's these very small, very negatively charged bundles of atoms which can ultimately change the fate of the cell and , by extension, the organism as a whole i.e you and me.

A diagram of a G-protein (or more accurately a G-protein coupled receptor (GPCR).*

Back to PI3 Kinases though. Changing cell activity is ultimately down to signalling, such as sending a hormone from the pancreas, through the blood stream to the  cells in question. Signals from outside the cell however have to somehow manage to  effect the internal workings of the cell. Some signals can just saunter in across the cell membrane, if they're small and of the correct charge. Many of the larger signals, like hormones, however have a specific protein with is a receptor sticking out of the cell membrane - and that's where the "G-protein" part comes in. G-proteins are a class of cell receptors which span the cell membrane, allowing the translation of signals which were received on the external face of the cell membrane to be transmitted into signals inside of the cell. G proteins only function when they are bound to their own unique highly specific signalling molecule - their ligand. 


G-proteins are a HUGE deal in biochemistry. More time and effort around the world goes into understanding G-proteins than many people care to imagine. Some are fairly well understood, whilst others are complete black boxes of understanding. One fairly well understood G-protein is rhodopsin, the protein responsible for all that vision you take for granted.


The general outline for this kind of signalling is the following:


signal binds to G-protein on the cell surface-> G-protein binds to PI3 Kinase inside of the cell -> activates PI3 Kinase -> PI3 Kinase phosphorylates lipid


So now you know what the G-proteins and phosphoinositide 3-kinase and singal transduction bits of the PhD title are about. As for the autophagy and cellular sorting I'm still in the dark about them.


*Image credits: http://rsc.riken.jp/eng/st_bio/process.html