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Institute of Advanced Study

Dr David Dryden

“I have nothing but praise for every aspect of the IAS.”

Dr David Dryden, University of Edinburgh

IAS Fellow at St John's College, Durham University (January - March 2016)

David Dryden is Reader in Biophysical Chemistry in the School of Chemistry at the University of Edinburgh and a former Royal Society University Research Fellow. He is a leading authority on the molecular biology of the DNA restriction and modification (RM) enzymes of prokaryotes and has published over one hundred research articles and reviews. In addition to analysing the structure and function of RM enzymes, his research has also covered a range of topics including the original proposal of dynamic allostery, the exploration of protein sequence space and the discovery of structural mimicry of DNA by proteins.

Starting from a first degree in chemical physics from the University of Glasgow, his work has always been at the boundaries between biology, chemistry and physics. He has been invited to attend several interdisciplinary meetings in recent years including the 2004 meeting on “Statistical Mechanics of Molecular and Cellular Biological Systems” at the Isaac Newton Institute of Mathematical Sciences, Cambridge, and the Durham University interdisciplinary meeting "Protein dynamics and function" held at Grey College and the IAS in 2013. In addition he held the Derek Brewer Visiting Fellowship to Emmanuel College, Cambridge in 2010 which provided a wonderful opportunity to interact with academics from a wide range of disciplines.

During the IAS Fellowship he proposes to investigate how the differing approaches of the physical sciences and the biological sciences have been utilised to advance our understanding of the living world. The RM phenomenon exhibited by the vast majority of bacterial species is particularly suited for investigating the synergy between the physical sciences and the biological sciences. RM was first reported in the early 1950s when the interactions between bacteria and bacterial viruses (bacteriophage) revealed an unusual pattern of “inheritance” as phage were passed between different strains of E. coli. This inheritance is a defined pattern of methylation (Modification) on the host genome which acts as a marker of "self" DNA and allows "foreign" phage DNA entering the cell to be identified and inactivated (Restriction). The Modification pattern due RM systems is one of the first examples of epigenetics. The Restriction function allows foreign DNA encoding new properties to be safely incorporated into the bacterium and drives bacterial evolution via horizontal gene transfer (unfortunately mostly know to humans as the cause of the spread of antibiotic resistance in bacteria). RM also provided the enzymes required for the development of gene cloning and biotechnology.

In addition, he hopes to explore the implications of some of his recent research on the evolution of the RM phenomenon with particular emphasis on the commonalities contained within the structures of the RM enzymes. No comprehensive picture of the evolution of RM currently exists but the results suggest that not only can one develop such a comprehensive model but also that RM is an ancient process and was important during the development of early life on the Earth. This latter aspect is much broader than the usual atomistic viewpoint used in research on RM and the wide interests of the IAS Fellows are likely to be very helpful.

The Fellowship at the IAS will provide a very stimulating environment for research and also facilitate easy access to colleagues in Physics, Chemistry, Biology and the Durham Biophysical Sciences Institute.

Public Lecture - What have Restriction Enzymes Ever Done for Us?

11th February 2016, 17:30 to 18:30, PG 20 Pemberton Buildings, Palace Green

The phenomenon of restriction-modification (RM) in bacteria was first elucidated in the early 1950’s and shown to be due to enzymes in the 1960’s. Defined target sequences within the bacterial DNA were maintained in a methylated (modified) form by these enzymes. Foreign DNA entering the host via a viral (bacteriophage) infection usually contained unmodified target sequences. The RM enzymes recognised this and cleaved the unmodified foreign DNA into fragments.

The ability to cleave DNA in a defined manner allowed the development in the 1970’s of modern molecular biology, genetic engineering and the multi-billion dollar biotechnology industry.

The rapid adoption of RM enzymes as the instrument of choice for DNA manipulation rather overshadowed the intrinsic importance of these RM enzyme systems to Nature and specifically to horizontal gene transfer, the major mechanism for rapid evolution of bacteria such as MRSA, and epigenetics, the marking of chromosomal DNA to control, for example, gene expression in higher organisms.

In this lecture Dr David Dryden will show how the enzymes are used in biotechnology and also address the fundamental importance of RM systems in Nature.
Open Access Reference: Highlights of the DNA cutters: a short history of the restriction enzymes. Loenen WAM, Dryden DTF, Raleigh EA, Wilson GG, Murray NE. Nucleic Acids Res. (2014) 42, 3-19.

Listen to the lecture in full.

Dr David Dryden Publications

Cooper, L.P, Roberts, G.A.; White, J.H., Luyten, Y.A., Bower, E.K.M., Morgan, R.D, Roberts, R.J., Lindsay, J.A., Dryden, T.F.D., (2017) DNA target recognition domains in the Type 1 restriction and modificatoin systems of Staphylococcus aureus, Nucleic Acids Research 45 (6) , pp 3395-3406

Kanwar, Nisha ; Roberts, Gareth A ; Cooper, Laurie P ; Stephanou, Augoustinos S., Dryden, D.T.F (2016) The evolutionary pathway from a biologically inactive polypeptide sequence to a folded, active structural mimic of DNA, Nucleic Acids Research 44 (9) , pp 4289-4303

IAS Insights Paper


Restriction enzymes, along with their counterparts the DNA methyltransferases, make up restriction-modification systems in almost all bacteria. The restriction enzymes have the ability to cut DNA into fragments. This has allowed experimenters to join such fragments together to make novel arrangements of DNA which had never before existed in nature. This ability to perform genetic engineering, developed from the 1970s onwards, has had an enormous influence on the modern world – establishing the biotechnology industry and transforming our understanding of biology and of medicine. Furthermore, the restriction enzymes have had an enormous impact on the rate of evolution of life on earth. They were almost certainly present in the earliest forms of bacterial cells some four billion years ago to control their uptake of DNA from their environment. If the restriction systems had had too much or too little control of this process then the rate of evolution of bacteria, and hence the time for the appearance of higher organisms such as ourselves, would likely have been greatly delayed – such that we might not yet exist on earth.