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Chemical Biology

Chemical Biology

Applying chemical methods to the understanding and manipulation of key biological processes.

Our research

Our research focuses on understanding the molecular mechanisms of biological processes. We employ a variety of biochemical, biophysical and cell-based functional studies of proteins to advance our understanding of the molecular basis of life.

We develop novel cyclic peptide and small molecule based chemical tools to achieve new opportunities for understanding and treating a diverse range of diseases.

Our research is at the interface of chemistry, biology and medicine, and many of our projects are highly collaborative. Research in this area focuses on:

  • Chemical Epigenetics
  • Peptide discovery platform
  • Infectious disease drug discovery

Research Themes

Chemical Epigenetics

Epigenetics are heritable alterations that are not due to changes in DNA sequence.

Our research seeks to develop chemical probes against the proteins that regulate epigenetic modifications. This will help us achieve a better understanding of epigenetic mechanisms and how they influence the expression of genes in health and disease.epigenetic mechanisms.

Current work in this area includes:

  • Biochemical and cellular studies of histone demethylases 
  • Investigating the inter-domain and combinatorial PTM cross-talk
  • Molecular recognition of PTMs by epigenetic proteins
  • Chemical probe development for epigenetic proteins including KDMs and PHD-finger domains.

 

Infectious disease drug discovery

We aim to discover and develop new small molecules to treat antibiotic resistant pathogenic bacterial infections.

Many of our molecules of interest are based on natural products derived from bacteria.

We identify new antibiotic natural products using:

  • synthetic organic chemistry
  • synthetic biology
  • molecular biology
  • bioinformatics
  • molecular analysis

We develop these further by understanding the mode of action of these molecules. We then apply these techniques to improve their pharmacokinetic properties for use as future drugs.

We collaborate with colleagues in microbiology, biochemistry, cell biology and analytical chemistry.

 

Peptide Discovery Platform

Cyclic peptides, which occupy the Goldilocks space between small molecules and large biologics, have emerged as a class of promising molecules in chemical biology and drug discovery.

We utilise a combination of peptide chemistry and peptide-array / mRNA-display technologies for substrate profiling, protein-protein interaction mapping, as well as to generate highly potent and selective ligands against our targets of interest.

Highlights in this area include:

  • Substrate profiling of epigenetic enzymes, development of potent and selective cyclic peptides inhibitors against epigenetic enzymes
  • Affinity cyclic peptide probes for oxygen sensing enzyme PHD2.

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