Prof Malcolm White:

Prof Malcolm White

Prof Malcolm White
Biomolecular Sciences Building
University of St Andrews
North Haugh
St Andrews
KY16 9ST

tel: 01334 463432
fax: 01334 462595
room: 307 Annexe

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Structural Biology
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.


Our lab is focussed on the molecular biology and evolution of proteins and pathways that manipulate nucleic acids, including helicases, nucleases and recombinases. We have particular interests in the CRISPR-Cas system of antiviral defence and DNA repair mechanisms. We utilise a combination of structural, molecular and micro-biology, biochemistry and bioinformatics.

The expertise within the Biomedical Sciences Research Complex allows us to utilise a wide variety of techniques including single-molecule TIRF microscopy, spectrometry and X-ray crystallography in these studies. Structure-function studies of archaeal repair proteins have important implications for the equivalent proteins in humans. The CRISPR-Cas system is a fascinating aspect of prokaryotic molecular biology with many fundamental research questions and exciting applications in genome engineering and biotechnology.

source: symbiosis

Recent Publications:

Recent publications listed in research@st-andrews
Peeters, E, Boon, M, Rollie, CJC, Willaert, RG, Voet, M, White, MF, Prangishvili, D, Lavigne, R & Quax, TEF 2017, 'DNA‐Interacting characteristics of the archaeal Rudiviral protein SIRV2_Gp1' Viruses, vol 9, no. 7, 190. DOI: 10.3390/v9070190
Han, W, Li, Y, Deng, L, Feng, M, Peng, W, Hallstrøm, S, Zhang, J, Peng, N, Liang, YX, White, MF & She, Q 2017, 'A type III-B CRISPR–Cas effector complex mediating massive target DNA destruction' Nucleic Acids Research, vol 45, no. 4, pp. 1983-1993. DOI: 10.1093/nar/gkw1274