Scheme: Wolfson Research Merit Awards
Organisation: University of Southampton
Dates: Aug 2013-Jul 2018
Summary: My research involves the synthesis of small molecules with chemical groups that can form hydrogen bonds, designed to selectively bind a particular type of anion. These molecules are organic molecules and prefer to be present in environments that are more like oil i.e. greasy, hydrophobic than water. We can use these
molecules in biological systems to mediate the transport of anions across cell membranes. These membranes have a hydrophobic ‘oily’ interior. As anions are charged they prefer to remain in water and it is difficult to extract them into the
interior of the membrane; in fact normally anions are transported through protein channels that span cell membranes. In patients suffering from diseases such as cystic fibrosis there are structural problems with some of these channels and
consequently chloride and bicarbonate anions cannot flow through them efficiently. This leads to problems such as the production of sticky mucus that causes lung infections. We are developing molecules that will restore the transport
of anions through cell membranes by selectively binding to them - so ‘wrapping them up’ in the oily, hydrophobic coat of the transporter molecule. The transporter–anion complex can then diffuse through the cell membrane with the
transporter releasing the anion on the other side. So the transporter molecule replaces the function of the faulty anion channel. These types of molecule also potentially have anti-cancer activity by perturbing chemical gradients within cancer cells so triggering the programmed death of the cell.
We have discovered a number of types of molecule capable of transporting anions through membranes and we are working to understand how to design the most efficient transporters that will work in very low dose. This will be essential if we are to use these compounds in patients.
If successful this work will provide a new, interdisciplinary approach for treating cystic fibrosis, cancer and other diseases.
Scheme: University Research Fellowship
Dates: Oct 1997-Sep 2005
Summary: This project summary is not available for publication.