Dr Sean Colloms
- Senior Lecturer (Institute of Molecular Cell & Systems Biology)
2008-Present: University of Glasgow
2000-2008: Wellcome Trust Senior Fellow in Basic Biomedical Research, University of Glasgow
1994-2000: Research Associate, Microbiology Unit, Biochemistry, University of Oxford
1992-1994: EMBO Fellow, Netherlands Cancer Institute, Amsterdam
1987-1990: PhD, University of Glasgow
1984-1987: BSc Natural Sciences (Genetics), University of Cambridge
Mechanism, function and applications of enzymes that cut and rejoin DNA.
Enzymes that break and then rejoin DNA are present in all domains of life and have a wide range of biological functions. My lab is interested in the mechanisms used by these enzymes. We are also developing these enzymes as tools that can be used for biotechnology as well as research.
Site-specific recombinases are enzymes that recognise specific short DNA sequences. They bring together two DNA sites that can be far apart in the genome, or on separate chromosomes, cut both sites and rejoin them in recombinant configuration. Site-specific recombinases have diverse biological roles that range from ensuring stable plasmid and chromosomes maintenance in bacteria to integrating viral DNA into the host genome. Bacteriophage integrases are tightly regulated so that bacteriophage DNA is inseted into its host genome just after infection but does not excise until the phage decides to re-enter the lytic cycle. We study the way in which this directionality is regulated by proteins called recombination directionality factors (RDFs). We also study the regulation of the Xer site-specific recombination that ensures chromosomes segregate evenly to both daughter cells during bacterial cell division.
Xer recombination at the plasmid resolution sites cer and psi is regulated by the DNA binding transcriptional regulators ArgR and ArcA, and the DNA-binding aminopeptidase PepA. This regulation ensures that only sites in the same orientation in a circular molecule recombine. The products are two circles of DNA linked together in a specific structure known as a 4-node catenane.
The directionality of bacteriophage integrases and their regulation by RDFs makes them ideal for building genetic switches. Recombination is used to flip the orientation of small DNA segments containing promoter sequences. This is used to control expression of genes placed on either side of the invertible DNA segment. Invertible DNA segments have two possible states and can therefore be used to encode binary numbers.We have recently published a paper showing how multiple switches could be used to make a counter that could count large numbers of events in living cells.
Cartoon showing how three inversion switches, each controlled by a different bacteriophage integrase could be used to control expression of GFP, RFP and CFP (green-, red- and cyan fluorescent proteins) and count up to 111 in binary (or seven in decimal numbers).
Another class of enzymes that cut and rejoin DNA are DNA transposases, enzymes that move segments of DNA known as transposons from on location to another in the genome. We study the mechanism of transposition of a transposon called ISY100 from Synechocystis. We are using ISY100 as a genetic tool to study gene function and chromosome structure.
All enzymes that cut and rejoin DNA change the topology of DNA, the way in which it is knotted, linked, tangled and twisted. DNA also becomes entagled during replication, so it is essential to remove all this tangling. Topoisomerases, the enzymes that untangle DNA, are important drug targets for cancer and bacterial infections. We study the tangling of DNA during site-specific recombination, the untangling of DNA after DNA replication by topoisomerases, and are working on new methods to study DNA topology.
Atomic force microscopy image of a 4-node catenan produced by Xer recombination. The DNA is absorbed onto a flat surface and imaged at nanometer scaled by tapping with a very small tip. Molecules are false coloured by height above the flat surface. (Image from James Provan, PhD student in association with Alice Pyne from the London Centre for Nanotechnology).
Grants and Awards listed are those received whilst working with the University of Glasgow.
- Knots in Nature - DNA, the Knotted Molecule of Life
2014 - 2020
- IGEM Support
Scottish Universities Life Sciences Alliance
2014 - 2015
- Generation of a large family of genetic logic gates for applications in bio-sensing and information processing
Biotechnology and Biological Sciences Research Council
2012 - 2014
- A platform for rapid and precise DNA module rearrangements in Synthetic Biology
Biotechnology and Biological Sciences Research Council
2012 - 2018
- We are studying the directionality of the large serine bacteriophage integrases and making mutants with improved properties for Synthetic Biology. Improvements include better directionality for genetic switches, counters, memory and DNA assembly.
- We are interested in how DNA is untangled after DNA replication. We ar using recombination by the large serine bacteriophage integrases to probe the structure of the genome.
- We are also interested in improving and purifying topoisomerases for biotechnology applications.
Projects for postgraduate students are available in any of the following areas:
- MSc in Biotechnology: Programme coordinator
- MSc in Biotechnology - Industrial and Environmental Microbiology: Course coordinator
- MSc in Biotechology - Syntehtic Biology: Course coordinator
- L4 DNA Option: Deputy Course coordinator and lecturer
- L4 Biotechnology Option: Deputy Course coordinator and lecturer
- L4 Industrial and Envrionmental Microbiology Option: Lecturer on bioremediation
Invited International Presentations
- 2006: Banff, Canada - ASM Conference on Mobile DNA
- 2004: Roscoffe, France - EMBO workshop on Transposition
Professional Learned Society
- 2005 - present: Society for General Microbiology - Member
- 2005 - present: American Society for Microbiology - Member
- 1995 - present: Genetics Society - Member
- 2000 - 2006: Wellcome Trust Senior Research Fellowship