Dr Ian Menz

Contact Details

Key Responsibilities

• Biotechnology and Bioinformatics

Teaching

• Biotechnology and Bioinformatics

Research

Research in my lab is focussed on determining the 3 dimensional structures of proteins using the technique of x-ray crystallography. The primary projects are:

i) 3D structures of malarial proteins as a basis for rational drug design
 

Malaria is currently the greatest cause of human mortality and our current arsenal of antimalarial drugs are faltering due to the emergence of drug resistant strains. Hence, there is a great demand for the development of new highly potent antimalarial drugs. The enzymes of de novo pyrimidine pathway are ideal targets for antimalarial drugs. Unlike the cells of the human host, which contain alternative salvage pathways, the malarial parasite is solely reliant on the de novo pathway for the synthesis of pyrimidine precursors. These precursors are essential for the synthesis of DNA and RNA and therefore crucial to the proliferation of the parasite. This difference in pyrimidine metabolism has an obvious advantage in development of a therapeutic drug, as complete specificity for the malarial enzyme is not a prerequisite, as the host could tolerate inhibition of its de novo pathway. The aim is to identify, clone and over-express in E. coli, enzymes of the de novo pyrimidine pathway from the human malarial parasite, Plasmodium falciparum. The recombinant protein will be utilised for the growth of protein crystals and subsequently atomic structures will be determined by x-ray crystallography. Examination of these structures will allow us to design new inhibitors or optimise the specificity and potency of present inhibitors.

ii) Investigation of the structure and function of ATP synthase
 

The biological molecule ATP is pivotal to life: its hydrolysis provides the energy to drive most cellular metabolic processes. ATP is synthesised during oxidative –phosphorylation or photo-phosphorylation by a multi-subunit assembly known as ATP synthase. This enzyme is unique as the physical rotation of a protein subunit drives ATP synthesis. This project involves structure determination to further our understanding of how physical rotation can drive chemical reactions, or conversely how chemical reactions can drive physical rotation that could be the basis of a molecular motor.

Other collaborative projects include, determining the structure of active laccase in collaboration with Dr. Lisa Martin, and the determination of the human dipetidyl peptidase DPP8, in collaboration with Dr. Catherine Abbott.
 

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