Dr Sean Colloms

Senior Lecturer (Molecular Biosciences)

telephone: 01413306236
email: Sean.Colloms@glasgow.ac.uk
pronouns: He/him/his

Room 504D Level 5, Institute of MC&SB, Bower Building, Glasgow G12 8QQ

Import to contacts

https://orcid.org/0000-0003-2369-8168

Biography

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

Research interests

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).

Research groups

Publications

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Number of items: 48.

2023

Abioye, J., Lawson‐Williams, M., Lecanda, A., Calhoon, B., McQue, A. L., Colloms, S. D. , Stark, W. M. and Olorunniji, F. J. (2023) High fidelity one‐pot DNA assembly using orthogonal serine integrases. Biotechnology Journal, 18(3), 2200411. (doi: 10.1002/biot.202200411) (PMID:36504358)

2020

Waraich, N. F., Jain, S., Colloms, S. D. , Stark, W. M. , Burton, N. P. and Maxwell, A. (2020) A novel decatenation assay for DNA topoisomerases using a singly-linked catenated substrate. BioTechniques, 69(5), pp. 356-362. (doi: 10.2144/btn-2020-0059) (PMID:33000631)

2019

Zhao, J., Pokhilko, A., Ebenhöh, O., Rosser, S. J. and Colloms, S. D. (2019) A single-input binary counting module based on serine integrase site-specific recombination. Nucleic Acids Research, 47(9), pp. 4896-4909. (doi: 10.1093/nar/gkz245) (PMID:30957849) (PMCID:PMC6511857)

Conte, E., Mende, L., Grainge, I. and Colloms, S. D. (2019) A mini-ISY100 transposon delivery system effective in γ proteobacteria. Frontiers in Microbiology, 10, 280. (doi: 10.3389/fmicb.2019.00280) (PMID:30873132) (PMCID:PMC6400869)

2018

Pokhilko, A., Ebenhöh, O., Stark, W. M. and Colloms, S. D. (2018) Mathematical model of a serine integrase-controlled toggle switch with a single input. Journal of the Royal Society: Interface, 15(143), 20180160. (doi: 10.1098/rsif.2018.0160) (PMID:29875284) (PMCID:PMC6030632)

2017

Olorunniji, F. J., McPherson, A. L., Rosser, S. J., Smith, M. C.M., Colloms, S. D. and Stark, W. M. (2017) Control of serine integrase recombination directionality by fusion with the directionality factor. Nucleic Acids Research, 45(14), pp. 8635-8645. (doi: 10.1093/nar/gkx567) (PMID:28666339) (PMCID:PMC5737554)

Olorunniji, F. J., Merrick, C., Rosser, S. J., Smith, M. C.M., Stark, W. M. and Colloms, S. D. (2017) Multipart DNA assembly using site-specific recombinases from the large serine integrase family. In: Eroshenko, N. (ed.) Site-Specific Recombinases: Methods and Protocols. Series: Methods in molecular biology (1642). Springer New York, pp. 303-323. ISBN 9781493971671 (doi: 10.1007/978-1-4939-7169-5_19)

2016

Pokhilko, A., Zhao, J., Ebenhöh, O., Smith, M. C.M., Stark, W. M. and Colloms, S. D. (2016) The mechanism of φC31 integrase directionality: experimental analysis and computational modelling. Nucleic Acids Research, 44(15), pp. 7360-7372. (doi: 10.1093/nar/gkw616) (PMID:27387286) (PMCID:PMC5009753)

Jones, D. D., Beal, J., Haddock-Angelli, T., Gershater, M., de Mora, K., Lizarazo, M., Hollenhorst, J., Rettberg, R. and iGEM Interlab Study Contributors, (2016) Reproducibility of fluorescent expression from engineered biological constructs in E. coli. PLoS ONE, 11(3), e0150182. (doi: 10.1371/journal.pone.0150182) (PMID:26937966) (PMCID:PMC4777433)

Pokhilko, A., Zhao, J., Stark, W. M. , Colloms, S. D. and Ebenhöh, O. (2016) A simplified mathematical model of directional DNA site-specific recombination by serine integrases. Journal of the Royal Society: Interface, 14, 20160618. (doi: 10.1098/rsif.2016.0618) (PMID:28077763) (PMCID:PMC5310728)

Merrick, C.A., Wardrope, C., Paget, J.E., Colloms, S.D. and Rosser, S.J. (2016) Rapid optimization of engineered metabolic pathways with serine integrase recombinational assembly (SIRA). In: O'Connor, S. E. (ed.) Synthetic Biology and Metabolic Engineering in Plants and Microbes Part A: Metabolism in Microbes. Series: Methods in enzymology (575). Elsevier, pp. 285-317. ISBN 9780128046166 (doi: 10.1016/bs.mie.2016.02.009)

2015

Bowyer, J., Zhao, J., Rosser, S., Colloms, S. and Bates, D. (2015) Development and experimental validation of a mechanistic model of in vitro DNA recombination. In: 37th Annual International Conference of the IEEE Engineering in Medicine and Biology Society (EMBC), Milan, Italy, 25-29 Aug 2015, pp. 945-948. (doi: 10.1109/EMBC.2015.7318519)

2014

Fogg, P. C.M., Colloms, S. , Rosser, S., Stark, M. and Smith, M. C.M. (2014) New applications for phage integrases. Journal of Molecular Biology, 426(15), pp. 2703-2716. (doi: 10.1016/j.jmb.2014.05.014) (PMID:24857859) (PMCID:PMC4111918)

Colloms, S.D. , Merrick, C.A., Olorunniji, F.J., Stark, W.M. , Smith, M.C.M., Osbourn, A., Keasling, J.D. and Rosser, S.J. (2014) Rapid metabolic pathway assembly and modification using serine integrase site-specific recombination. Nucleic Acids Research, 42(4), e23. (doi: 10.1093/nar/gkt1101) (PMID:24225316) (PMCID:PMC3936721)

2013

Colloms, S.D. (2013) Leucyl aminopeptidase PepA. In: Rawlings, N.D. and Salvesen, G. (eds.) Handbook of Proteolytic Enzymes. Academic Press, pp. 1484-1492. ISBN 9780123822192 (doi: 10.1016/B978-0-12-382219-2.00334-3)

Colloms, S.D. (2013) The topology of plasmid-monomerizing Xer site-specific recombination. Biochemical Society Transactions, 41(2), pp. 589-594. (doi: 10.1042/BST20120340)

2012

Olorunniji, F. J., Buck, D. E., Colloms, S. D. , McEwan, A. R., Smith, M. C. M., Stark, W. M. and Rosser, S. J. (2012) Gated rotation mechanism of site-specific recombination by ϕC31 integrase. Proceedings of the National Academy of Sciences of the United States of America, 109(48), pp. 19661-19666. (doi: 10.1073/pnas.1210964109)

Colloms, S. and Renault, S. (2012) Modified transposases for site-directed insertion of transgenes. In: Renault, S. and Duchateau, P. (eds.) Site-Directed Insertion of Transgenes. Series: Topics in current genetics, 23 (23). Springer, pp. 241-265. ISBN 9789400745308 (doi: 10.1007/978-94-007-4531-5_9)

2010

Feng, X., Bednarz, A.L. and Colloms, S.D. (2010) Precise targeted integration by a chimaeric transposase zinc-finger fusion protein. Nucleic Acids Research, 38(4), pp. 1204-1216. (doi: 10.1093/nar/gkp1068)

2009

Richardson, J.M., Colloms, S.D. , Finnegan, D.J. and Walkinshaw, M.D. (2009) Molecular architecture of the Mos1 paired-end complex: the structural basis of DNA transposition in a eukaryote. Cell, 138(6), pp. 1096-1108. (doi: 10.1016/j.cell.2009.07.012)

Trigueros, S., Tran, T., Sorto, N., Newmark, J., Colloms, S.D. , Sherratt, D.J. and Tolmasky, M.E. (2009) mwr Xer site-specific recombination is hypersensitive to DNA supercoiling. Nucleic Acids Research, 37(11), pp. 3580-3587. (doi: 10.1093/nar/gkp208)

2008

MacDonald, A.I., Lu, Y., Kilbride, E.A., Akopian, A. and Colloms, S.D. (2008) PepA and ArgR do not regulate Cre recombination at the bacteriophage P1 loxP site. Plasmid, 59(2), pp. 119-126. (doi: 10.1016/j.plasmid.2007.12.001) (PMID:18226834) (PMCID:PMC2409434)

2007

Feng, X. and Colloms, S.D. (2007) In vitro transposition of ISY100, a bacterial insertion sequence belonging to the Tc1/mariner family. Molecular Microbiology, 65(6), pp. 1432-1443. (doi: 10.1111/j.1365-2958.2007.05842.x)

2006

Akopian, A., Gourlay, S., James, H. and Colloms, S. (2006) Communication between accessory factors and the Cre recombinase at hybrid psi-loxP sites. Journal of Molecular Biology, 357, pp. 1394-1408. (doi: 10.1016/j.jmb.2006.01.050)

2005

Reijns, M., Lu, Y., Leach, S. and Colloms, S. (2005) Mutagenesis of PepA suggests a new model for the Xer/cer synaptic complex. Molecular Microbiology, 57, pp. 927-941. (doi: 10.1111/j.1365-2958.2005.04716.x)

Vazquez, M., Colloms, S. and Sumners, D. (2005) Tangle analysis of Xer recombination reveals only three solutions, all consistent with a single three-dimensional topological pathway. Journal of Molecular Biology, 346, pp. 493-504. (doi: 10.1016/j.jmb.2004.11.055)

2004

Colloms, S. D. (2004) Leucyl aminopeptidase PepA. In: Barrett, A.J., Woessner, J.F. and Rawlings, N.D. (eds.) Handbook of Proteolytic Enzymes [2nd ed.]. Volume 1: Aspartic and Metallo Peptidases. Elsevier, pp. 905-910. ISBN 9780120796113 (doi: 10.1016/B978-0-12-079611-3.50277-9)

Gourlay, S. and Colloms, S. (2004) Control of Cre recombination by regulatory elements from Xer recombination systems. Molecular Microbiology, 52, pp. 53-65. (doi: 10.1111/j.1365-2958.2003.03962.x)

2002

Bregu, M., Sherratt, D.J. and Colloms, S.D. (2002) Accessory factors determine the order of strand exchange in Xer recombination at psi. EMBO Journal, 21(14), pp. 3888-3897. (doi: 10.1093/emboj/cdf379) (PMID:12110600) (PMCID:PMC126124)

2000

Tolmasky, M. E., Colloms, S. , Blakely, G. and Sherratt, D. J. (2000) Stability by multimer resolution of pJHCMW1 is due to the Tn1331 resolvase and not to the Escherichia coli Xer system. Microbiology, 146(3), pp. 581-589. (doi: 10.1099/00221287-146-3-581) (PMID:10746761)

Barre, F.-X., Aroyo, M., Colloms, S. D. , Helfrich, A., Cornet, F. and Sherratt, D. J. (2000) FtsK functions in the processing of a Holliday junction intermediate during bacterial chromosome segregation. Genes and Development, 14(23), pp. 2976-2988. (doi: 10.1101/gad.188700) (PMID:11114887) (PMCID:PMC317095)

1999

Bath, J., Sherratt, D. J. and Colloms, S. D. (1999) Topology of Xer recombination on catenanes produced by Lambda integrase. Journal of Molecular Biology, 289(4), pp. 873-883. (doi: 10.1006/jmbi.1999.2804) (PMID:10369768)

Strater, N., Sherratt, D. J. and Colloms, S. D. (1999) X-ray structure of aminopeptidase A from Escherichia coli and a model for the nucleoprotein complex in Xer site-specific recombination. EMBO Journal, 18(16), pp. 4513-4522. (doi: 10.1093/emboj/18.16.4513) (PMID:10449417) (PMCID:PMC1171526)

1998

Colloms, S. D. , Alen, C. and Sherratt, D. J. (1998) The ArcA/ArcB two-component regulatory system of Escherichia coli is essential for Xer site-specific recombination at psi. Molecular Microbiology, 28(3), pp. 521-530. (doi: 10.1046/j.1365-2958.1998.00812.x) (PMID:9632255)

1997

Zerbib, D., Colloms, S. D. , Sherratt, D. J. and West, S. C. (1997) Effect of DNA topology on holliday junction resolution by Escherichia coli RuvC and bacteriophage T7 endonuclease I. Journal of Molecular Biology, 270(5), pp. 663-673. (doi: 10.1006/jmbi.1997.1157) (PMID:9245595)

Colloms, S. D. , Bath, J. and Sherratt, D. J. (1997) Topological selectivity in Xer site-specific recombination. Cell, 88(6), pp. 855-864. (doi: 10.1016/S0092-8674(00)81931-5) (PMID:9118228)

Alen, C., Sherratt, D. J. and Colloms, S. D. (1997) Direct interaction of aminopeptidase A with recombination site DNA in Xer site-specific recombination. EMBO Journal, 16(17), pp. 5188-5197. (doi: 10.1093/emboj/16.17.5188) (PMID:9311979) (PMCID:PMC1170151)

1996

Colloms, S.D. , McCulloch, R., Grant, K., Neilson, L. and Sherratt, D.J. (1996) Xer-mediated site-specific recombination in vitro. EMBO Journal, 15(5), pp. 1172-1181. (PMID:8605888) (PMCID:PMC450016)

1995

van Steenbergen, T.J. M., Colloms, S. D. , Hermans, P. W.M., de Graaff, J. and Plasterk, R. H.A. (1995) Genomic DNA fingerprinting by restriction fragment end labeling. Proceedings of the National Academy of Sciences of the United States of America, 92(12), pp. 5572-5576. (doi: 10.1073/pnas.92.12.5572) (PMID:7777550) (PMCID:PMC41738)

Sherratt, D. J., Arciszewska, L. K., Blakely, G., Colloms, S. , Grant, K., Leslie, N. and McCulloch, R. (1995) Site-specific recombination and circular chromosome segregation. Philosophical Transactions of the Royal Society B: Biological Sciences, 347(1319), pp. 37-42. (doi: 10.1098/rstb.1995.0006) (PMID:77468)

1994

van Luenen, H. G.A.M., Colloms, S. D. and Plasterk, R. H.A. (1994) The mechanism of transposition of Tc3 in C. elegans. Cell, 79(2), pp. 293-301. (doi: 10.1016/0092-8674(94)90198-8) (PMID:7954797)

McCulloch, R., Coggins, L.W., Colloms, S.D. and Sherratt, D.J. (1994) Xer-mediated site-specific recombination at cer generates Holliday junctions in vivo. EMBO Journal, 13(8), pp. 1844-1855. (PMID:8168483) (PMCID:PMC395024)

Colloms, S. D. , van Luenen, H. G.A.M. and PIasterk, R. H.A. (1994) DNA binding activities of the Caenorhabditis elegans Tc3 transposase. Nucleic Acids Research, 22(25), pp. 5548-5554. (doi: 10.1093/nar/22.25.5548) (PMID:7838706) (PMCID:PMC310115)

1993

van Luenen, H.G., Colloms, S.D. and Plasterk, R.H. (1993) Mobilization of quiet, endogenous Tc3 transposons of Caenorhabditis elegans by forced expression of Tc3 transposase. EMBO Journal, 12(6), pp. 2513-2520. (PMID:8389698) (PMCID:PMC413489)

Sherratt, D., Blakely, G., Burke, M., Colloms, S. , Leslie, N., McCulloch, R. , May, G. and Roberts, J. (1993) Site-specific recombination and the partition of bacterial chromosomes. In: Heslop-Harrison, J. and Flavell, R. (eds.) The Chromosome. BIOS Scientific Publishers: Oxford, pp. 25-41. ISBN 1872748325

1991

Blakely, G., Colloms, S. , May, G. , Burke, M. and Sherratt, D. (1991) Escherichia coli XerC recombinase is required for chromosomal segregation at cell division. New Biologist, 3(8), pp. 789-798. (PMID:1931824)

1990

Colloms, S. D. , Sykora, P., Szatmari, G. and Sherratt, D. J. (1990) Recombination at ColE1 cer requires the Escherichia coli xerC gene product, a member of the lambda integrase family of site-specific recombinases. Journal of Bacteriology, 172(12), pp. 6973-6980. (doi: 10.1128/jb.172.12.6973-6980.1990) (PMID:2254268) (PMCID:PMC210817)

1989

Stirling, C.J., Colloms, S.D. , Collins, J.F., Szatmari, G. and Sherratt, D.J. (1989) xerB, an Escherichia coli gene required for plasmid ColE1 site-specific recombination, is identical to pepA, encoding aminopeptidase A, a protein with substantial similarity to bovine lens leucine aminopeptidase. EMBO Journal, 8(5), pp. 1623-1627. (PMID:2670557) (PMCID:PMC400995)

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