The general theme of my current research is to understand at the molecular level how cells transport small molecules into and out of the living cell. Transport occurs at the nanometre scale, with the conduction pathways having typical lengths of 2-10 nm and diameters ranging from the one of a water molecule (ca 0.28 nm) to 1 nm. Pores of these dimensions can be found in many systems (see right hand illustration, from top to bottom): Water transporting protein Aqp1 (pdb: 1H6I), a zeolite (class AFI) and a single-wall carbon nanotube; at the bottom a model pore is displayed that tries to capture the essential characteristics of the real pores.
The subject of my DPhil thesis was Gating mechanisms of ion channels. I investigated a 'hydrophobic gating mechanism' which appears to be realised in the nicotinic acetylcholine receptor ( nAChR) and possibly other ion channels such as MscS.
A cell is a very complex system. It is encapsulated by a lipid membrane that is impermeable to most substances that the cell needs for functioning, especially polar species like water or ions or non-polar molecules like small sugars. In order to facilitate transport of these molecules the cell membrane contains a vast array of specialised proteins that either form "holes" or act as translocating machines. Because the process of staying alive depends on a finely regulated network of interactions which can depend sensitively on the concentrations of various solutes, transport must be tightly controlled.
Nature implements control by a twofold approach. Firstly, most transport proteins are highly selective, i.e. they are only permeable for a very limited range of permeators (for example, the potassium channel KcsA is 1000 times more permeable to K+ ions than to the very similar Na+ ions). Secondly, the protein can sense an external signal (e.g. a change in voltage across the membrane, a change in pH, a signal molecule) and correspondingly interrupt or allow the flow of the permeators, i.e. the "hole" can be open or closed. This is called gating.
Pores that are selective and have a gating mechanism are called channels; often, un-gated but selective protein-pores are referred to as porins. A third class of transport-proteins do not resemble holes but are complicated pumps which can translocate their substrates against a concentration gradient by harnessing the chemical power stored in ATP or an electrochemical gradient across the membrane.Last modified: 2010-09-01 by Oliver Beckstein