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Dr David Miller 

I am interested in the use of synthetic organic chemistry as applied to the solution of biological problems and vice versa.  The understanding of how Nature’s macromolecules such as proteins and DNA work and interact with one another can often be probed by use of small organic molecules.  Such molecules are often not available from the natural pool and so the synthetic chemist is central to solving such problems.  Similarly, synthetic chemistry although well capable of preparing the most complex and intricate of molecules can often only do so at great expense of time and resources. Natural systems, if harnessed correctly offer the opportunity to construct molecules of such complexity much more quickly and efficiently.

Inositol monophoshphatase.

Inositol monophosphatase is an enzyme that is involved in a crucial signal transduction pathway within our cells that has been implicated as a target for drugs that treat bipolar disorders.  We are interested in the study of the mechanism of action of this enzyme and in the discovery of new inhibitors that may ultimately lead to better treatments for this debilitating condition.

Diagram showing the natural substrate inositol-1-phosphate bound at the active site of IMPase.


Calpains are cysteine proteases that are activated by calcium ions.  mu-Calpain is a member of this family of enzymes that appears to have a key role in cell-membrane expansion and hence motility of white blood cells (neutrophils).  Development of potent and selective mu-calpain inhibitors may lead to a treatment for a variety of autoimmune diseases such as osteoarthritis.

Mercaptoacrylate PD150606 bound to domain VI of calpain.

Biosynthesis of terpenoids

Terpenes are the largest and most diverse group of natural products but originate from only a tiny group of prenyl diphosphate precursors.  Diversity is generated in nature by the structurally similar terpene cyclases that form many different products from each prenyl diphosphate.  By a combination of chemical synthesis, enzymology and molecular biology we seek to understand how such diversity can be created by enzymes that share a common fold.

Diagram showing the sesquiterpene precursor farnesyl diphosphate and some of the downstream sesquiterpene products.