I have spent much of the last decade in Cambridge, UK working at the MRC Centre for Protein Engineering where I developed a strong background in molecular biology, protein engineering, state-of-the-art biophysical methodologies and structural biology. Historically, my research focused on using a highly multi-disciplinary approach to dissect the rules that allow a linear sequence of amino acids to specify the spontaneous folding of polypeptides into unique 3D structures that, in turn, mediate biological function.

The chemical principles that guide protein folding are, however, identical to those that determine all bio-molecular processes, including protein-protein interactions, protein misfolding, virus assembly and replication. Thus, my academic background and experimental approaches are well placed to provide novel and exciting insights into these processes, which can be very challenging to study at high-resolution using classical cell-biology based approaches. These areas are not just of academic interest, but have practical implications - a detailed understanding of the molecular basis of neurodegenerative and infectious diseases will impact on the development of much needed, novel therapeutics.

The drug pipelines of large pharmaceutical companies, who typically discover drugs using high-throughput screening of large compound collections, are currently drying up and existing approaches are no longer working well for new targets. This factor, combined the failure of structural genomics and proteomics to revolutionize the drug discovery process, necessitates the use of other strategies to develop new therapies for challenging and newly emerging drug targets. This can only be achieved through a more detailed understanding of protein structure-function, better characterization of therapeutics targets and the application of more modern approaches to drug discovery.

With this in mind, my laboratory currently focuses on using protein engineering, biophysical methods and structural biology to tackle three main areas:

1)      1) Detailed dissection of the molecular interactions important to viral replication with a view to understanding these processes at the atomic level (e.g. current projects include studies of human hepatitis and papilloma viruses).

2) Identification of novel therapeutic targets and development of novel inhibitors using fragment-based lead discovery and rational design of peptidomimetic inhibitors.

3)Design/optimization of biotherapeutics (e.g. optimization of yield, stability, solubility and efficacy).

My laboratory is extremely well equipped. I have state of the art: (i) protein purification facilities; (ii) large-scale bioreactor for mammalian and insect cell cultures; (iii) a combinatorial surface plasmon resonance platform; (iv) sequential-mixing stopped flow fluorimeter; (v) multi-angle laser light scattering instrumentation. When combined with other excellent facilities within the institute, including high-end mass spectrometers, circular dichroism spectrapolarimeter and isothermal titration calorimetry - and guaranteed access to large-scale NMR facilities in the EU - we are well placed to tackle pretty much any angle of protein structure-function, drug design and fragment screening.

Prof. Pauline Rudd (NIBRT, UCD) - glycobiology

Prof. Dominic Walsh (SBBS, UCD) - Aggregation of Alzheimer's peptides

Dr. Stefan M. V. Freund (MRC, Cambridge, UK) - high molecular weight solution NMR/dynamics

Profs. Timothy Block and Anand Mehta (Hepatitis Foundation and Drexel Uni, Pennsylvannia, USA) - virology

Prof. Hartmut Oschkinat (FMP, Berlin, Germany) - magic angle spinning NMR

Drs. John Berriman & Peter Rosenthal (MRC, National Institute of Medical Research, London, UK) - electron microscopy

Dr. Amir Khan (Trinity College Dublin) - X-ray crystallography

Dr. Luca Pellegrini (University of Cambridge, Biochemistry Department) - characterisation of high molecular weight complexes involved in human breast cancer

Prof. Per Jemth (Uppsala University) - characterisation of human papilloma virus protein-protein interactions that cause cervical cancer

Dr. Faaizah Khan

Dr. Tim D. Sharpe

Dr. Miriana Petrovic

Dr. Roberto Canales

Dr. Pamela J. Schartau