Leyla Hussein's Research Page

Current Research: Rational design of peptide-based self assembling enzymes and ion channels

I am working jointly with Professor Leo Brady's lab (School of Biochemistry) to explore a new protein structure (CC-hex) which comprises 6 copies of a de novo designed peptide folded into alpha-helices and assembled into a parallel helical bundle.

My project combines computational modelling, structural analysis (CD spectroscopy, AUC and X-ray defraction) and activity characterisation by UV spectroscopy to explore possible active sites within the CC-hex structure. Initially, the enzyme design project will focus on esterase activity, involving strategic mutations within the CC-hex pore. Further work will concentrate on surface mutations to make CC-hex membrane soluble for ion channel targets.

The long term objective is to develop synthetic forms of biomolecules that can be targeted to desired enzymatic and ion-channel functions.

Previous Research

As part of my year in industry placement at AstraZeneca, I worked within the Safety Pharmacolog Department as part of the Cardiac Safety Group. My project worked alongside the Discovery Enabling Capabilities and Sciences (DECS) team to provide an in vitro calibration data set for an in silico model. This model has the potential ability to predict a compounds effect on the cardiac action potential in canine midmyocardial cells when provided with the IC50 data for each of the 5 key ion channels (hNav1.5, hCav1.2, hIto, Kv4.3-hKChIP2.2, hKv7.1-hKCNE1, and hKv11.1).

Following this, my undergraduate project at the University of Bristol involved in silico docking studies of Disopyramide on a hERG (hKv11.1) homology model.

Publications

[1] "Molecular determinants of hERG potassium channel inhibition by disopyramide." A El Harchi, YH Zhang, L Hussein, CE Dempsey and JC Hancox Journal of Molecular and Cellular Cardiology (In press) 2011

[2] "In silico canine cardiac midmyocardial action potential duration model: Suitable for early assessment?" L Hussein, MR Davies, H Mistry, CE Pollard, J Swinton, JP Valentin and N Abi-Gerges Journal of Pharmacological and Toxicological Methods 64 p.e7, 2011

[3] "Systems biology in drug safety assessment: use of a recalibrated Hund-Rudy model to predict effect of novel drug compounds on action potential duration" MR Davies, H Mistry, L Hussein, N Abi-Gerges, CE Pollard and J Swinton Computing in Cardiology 37: pp821-824, 2010.