Prof Malcolm White:
Prof Malcolm White
Biomolecular Sciences Building
University of St Andrews
tel: 01334 463432
fax: 01334 462595
room: 307 Annexe
School of Biology
Biomedical Sciences Research Complex
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DNA Repair Proteins and Pathways
All organisms invest considerable resources in the maintenance and repair of their genetic material, DNA. This is unsurprising, as the consequences of DNA damage can be mutation, cell death and, in humans, cancer. The archaea are a group of micro-organisms often found in extreme environments. Although they resemble bacteria in most respects, they have key similarities to eukaryotes, including humans, in the way that they process information including their DNA replication and repair pathways. This unexpected relationship makes the archaea an attractive model for the study of DNA repair pathways that are very complex in humans. Archaeal proteins tend to be simpler and are often more stable than their human counterparts, making them ideal for structural and biochemical studies. We utilise a variety of interdisciplinary techniques ranging from microbiology and genetics through biochemistry and molecular biology to biophysics and structural biology. In addition to the intrinsic interest in archaeal DNA repair, these thermostable proteins have potential applications in biotechnology, and our studies can shed light on the equivalent pathways for DNA repair in humans.
The CRISPR system for antiviral defence
CRISPR is a recently discovered antiviral defence system in prokaryotes. Viral DNA incorporated in the host genome is used to generate interfering CRISPR-RNAs that guide CRISPR associated (CAS) proteins to target and degrade invading viral nucleic acid. The CRISPR pathway is complex with many different enzymes involved and several aspects are very poorly understood. We are investigating the molecular mechanisms of the CRISPR system in Sulfolobus solfataricus, which has three different mechanisms to target and degrade viral nucleic acid.