{"id":203,"date":"2022-11-28T11:03:27","date_gmt":"2022-11-28T11:03:27","guid":{"rendered":"https:\/\/biology.st-andrews.ac.uk\/research\/?post_type=research_theme&#038;p=203"},"modified":"2022-11-28T14:28:26","modified_gmt":"2022-11-28T14:28:26","slug":"enzymology","status":"publish","type":"research_theme","link":"https:\/\/biology.st-andrews.ac.uk\/research\/research-theme\/enzymology\/","title":{"rendered":"Enzymology"},"content":{"rendered":"","protected":false},"excerpt":{"rendered":"","protected":false},"featured_media":206,"parent":0,"menu_order":0,"template":"","class_list":["post-203","research_theme","type-research_theme","status-publish","has-post-thumbnail","hentry"],"jetpack_sharing_enabled":true,"related_groups":[{"group_members":"<strong>Current lab members:<\/strong>\r\n\r\n&nbsp;\r\n\r\n<strong>Clarissa Melo Czekster<\/strong><span>\u00a0<\/span>\u2013 Group Leader\r\n\r\n<img class=\"alignleft size-medium wp-image-99\" src=\"https:\/\/czeksterlab.wp.st-andrews.ac.uk\/files\/2018\/03\/CMC-photo-300x225.jpg\" sizes=\"(max-width: 300px) 100vw, 300px\" srcset=\"https:\/\/czeksterlab.wp.st-andrews.ac.uk\/files\/2018\/03\/CMC-photo-300x225.jpg 300w, https:\/\/czeksterlab.wp.st-andrews.ac.uk\/files\/2018\/03\/CMC-photo-768x576.jpg 768w, https:\/\/czeksterlab.wp.st-andrews.ac.uk\/files\/2018\/03\/CMC-photo-1024x768.jpg 1024w, https:\/\/czeksterlab.wp.st-andrews.ac.uk\/files\/2018\/03\/CMC-photo-620x465.jpg 620w\" alt=\"\" width=\"300\" height=\"225\" \/>I am from Porto Alegre, Rio Grande do Sul, Brazil, where I went to college to obtain a BSc in Molecular Biology (2001-2004), a teaching degree in Biological Sciences (2003-2005), and an MSc in Biochemistry (2006-2008) at the Federal University of Rio Grande do Sul (UFRGS). I moved to New York city for a PhD in enzymology at Albert Einstein College of Medicine with John S. Blanchard (2008-2012). After my PhD I went to Yale University to join Alanna Schepartz\u2019s laboratory as a postdoc, working with beta-amino acids and the ribosome (2012-2014). I moved to the UK as a postdoc in Jim Naismith\u2019s group at the University of St Andrews (2015-2017), where I worked with toxic cyclic peptides from mushroom and cyanobacteria.\r\n\r\nSince 2017 I have been an independent research fellow in St Andrews, and in 2018 I was awarded a Sir Henry Dale Fellowship from the Wellcome Trust to establish my lab in St Andrews.\r\n\r\nClarissa Czekster on<span>\u00a0<\/span><a href=\"http:\/\/scholar.google.co.uk\/citations?hl=en&amp;user=_Mu0cjEAAAAJ&amp;view_op=list_works\">Google Scholar<\/a>\r\n\r\nOrcid: <a href=\"https:\/\/orcid.org\/0000-0002-7163-4057\">https:\/\/orcid.org\/<span>0000-0002-7163-4057<\/span><\/a>\r\n\r\n&nbsp;\r\n\r\n<img class=\"wp-image-258 alignright\" src=\"https:\/\/czeksterlab.wp.st-andrews.ac.uk\/files\/2021\/09\/Christopher-Harding-photo-2021.jpg\" sizes=\"(max-width: 212px) 100vw, 212px\" srcset=\"https:\/\/czeksterlab.wp.st-andrews.ac.uk\/files\/2021\/09\/Christopher-Harding-photo-2021.jpg 359w, https:\/\/czeksterlab.wp.st-andrews.ac.uk\/files\/2021\/09\/Christopher-Harding-photo-2021-223x300.jpg 223w\" alt=\"\" width=\"212\" height=\"284\" \/>\r\n\r\n&nbsp;\r\n\r\n<strong>Christopher J. Harding<\/strong><span>\u00a0<\/span>\u2013 Postdoctoral fellow\r\n\r\nI am\u00a0 from Preston, where I grew up before moving to Birmingham to obtain an MSci in Biochemistry from the University of Birmingham (2010-2014). I stayed on at the University of Birmingham for my PhD (2014-2018), where I worked in the laboratory of Dr Andrew Lovering. My PhD, titled \u201cStructural and Functional Investigations of\u00a0<i>Bdellovibrio bacteriovorus\u00a0<\/i>Lifecycle Proteins\u201d involved characterising a number of unrelated protein targets. I have now moved to the University of St. Andrews to begin my first Postdoc position in the laboratory of Dr Clarissa M Czekster\r\n\r\nOrcid: <a href=\"https:\/\/orcid.org\/0000-0003-0388-6460\">https:\/\/orcid.org\/0000-0003-0388-6460<\/a>\r\n\r\n&nbsp;\r\n\r\n<img class=\"wp-image-212 alignright\" src=\"https:\/\/czeksterlab.wp.st-andrews.ac.uk\/files\/2020\/06\/Rebecca-768x1024.jpg\" sizes=\"(max-width: 202px) 100vw, 202px\" srcset=\"https:\/\/czeksterlab.wp.st-andrews.ac.uk\/files\/2020\/06\/Rebecca-768x1024.jpg 768w, https:\/\/czeksterlab.wp.st-andrews.ac.uk\/files\/2020\/06\/Rebecca-225x300.jpg 225w, https:\/\/czeksterlab.wp.st-andrews.ac.uk\/files\/2020\/06\/Rebecca-620x827.jpg 620w, https:\/\/czeksterlab.wp.st-andrews.ac.uk\/files\/2020\/06\/Rebecca.jpg 960w\" alt=\"\" width=\"202\" height=\"269\" \/>\r\n\r\n&nbsp;\r\n\r\n<strong>Rebecca Cornwell<\/strong><span>\u00a0<\/span>\u2013 Public Engagement Officer\r\n\r\nOriginally from St Andrews, I graduated from the University of Durham with a BSc (Hons) in Applied Physics (1994) followed by a PGCE (with Qualified Teacher Status) from the University of Exeter (1995). I began teaching in Dorset, moving to Cambridge and then back home to St Andrews. I obtained Full Registration with the GTCS and, as well as, returning to teaching in Fife, I have held roles including Education Tutor at St Andrews Botanic Garden. Starting from studying Open University short courses, I went on to graduate with an MRes in Environmental Biology with Distinction (Conversion Course, 2011) from the University of St Andrews. I then graduated from the University of Dundee with an MPhil in Applied Mathematics (Mathematical Biology) for a thesis entitled \u201cThe Dynamics of Natural Enemy Resistance in Aphid Populations\u201d (2016). I am a Member of the Institute of Physics, Chartered Physicist and Member of the Royal Entomological Society. I have joined the Czekster lab as Public Engagement Officer for the \u201cAntibiotics under our feet\u201d project.\r\n\r\n&nbsp;\r\n\r\n<img class=\"alignleft wp-image-218\" src=\"https:\/\/czeksterlab.wp.st-andrews.ac.uk\/files\/2021\/02\/Gary2.jpg\" sizes=\"(max-width: 188px) 100vw, 188px\" srcset=\"https:\/\/czeksterlab.wp.st-andrews.ac.uk\/files\/2021\/02\/Gary2.jpg 432w, https:\/\/czeksterlab.wp.st-andrews.ac.uk\/files\/2021\/02\/Gary2-182x300.jpg 182w\" alt=\"\" width=\"188\" height=\"310\" \/>\r\n\r\n&nbsp;\r\n\r\n<strong>Peijun (Gary) Tang<\/strong><span>\u00a0<\/span>\u2013 Research Associate \u2013 Biocatalysis\r\n\r\nI am from Shanghai China, where I attended a cooperation program between Shanghai University of Traditional Chinese Medicine and London Metropolitan University, obtaining a BSc in Pharmacy and Herbal Medicinal Science (2011-2015). Then I completed my MSc in Pharmaceutical Science &amp; Medicinal Chemistry at Loughborough University (2015 \u2013 2016). Then, I moved to Edinburgh, where I started my PhD with Prof. Campopiano\u2019s group (2016 \u2013 2020) funded by Edinburgh Global Research Scholarship focusing on the \u2018Exploring the structure and function of key enzymes involved in microbial sphingolipid biosynthesis\u2019. Based on the interest on enzymology, I started my first job in the Dr. Clarissa M Czekster lab in the University of St. Andrews from 2021.\r\n\r\nOrcid:\u00a0<a href=\"https:\/\/orcid.org\/0000-0003-2647-9913\">https:\/\/orcid.org\/0000-0003-2647-9913<\/a>\r\n\r\n&nbsp;\r\n\r\n&nbsp;\r\n\r\n<img class=\"wp-image-193 alignright\" src=\"https:\/\/czeksterlab.wp.st-andrews.ac.uk\/files\/2019\/10\/Charlene-Ogilvie-Science-Profile-Pic-153x300.jpg\" alt=\"\" width=\"194\" height=\"381\" \/>\r\n\r\n&nbsp;\r\n\r\n<strong>Charlene E. Ogilvie<\/strong><span>\u00a0<\/span>\u2013 PhD student\r\n\r\nI am from Dundee, where I attended college to obtain a Higher National Certificate (HNC) in Applied Science and a Higher National Diploma (HND) in Biomedical Science. I have since completed an integrated masters in biochemistry \u2013 MBiochem (Hons) \u2013 at the University of St Andrews (2014-2019) and have chosen to stay here to complete my postgraduate studies in the laboratory of Dr Clarissa M. Czekster. My PhD project will aim to identify whether cyclic peptides influence interspecies interactions in the mouth microbiota.\r\n\r\n&nbsp;\r\n\r\n&nbsp;\r\n\r\n&nbsp;\r\n\r\n&nbsp;\r\n\r\n<img class=\"wp-image-197 alignleft\" src=\"https:\/\/czeksterlab.wp.st-andrews.ac.uk\/files\/2019\/11\/Emmajay-Sutherland-photo-208x300.jpg\" sizes=\"(max-width: 224px) 100vw, 224px\" srcset=\"https:\/\/czeksterlab.wp.st-andrews.ac.uk\/files\/2019\/11\/Emmajay-Sutherland-photo-208x300.jpg 208w, https:\/\/czeksterlab.wp.st-andrews.ac.uk\/files\/2019\/11\/Emmajay-Sutherland-photo-768x1109.jpg 768w, https:\/\/czeksterlab.wp.st-andrews.ac.uk\/files\/2019\/11\/Emmajay-Sutherland-photo-709x1024.jpg 709w, https:\/\/czeksterlab.wp.st-andrews.ac.uk\/files\/2019\/11\/Emmajay-Sutherland-photo-620x895.jpg 620w\" alt=\"\" width=\"224\" height=\"323\" \/>\r\n\r\n&nbsp;\r\n\r\n<strong>Emmajay Sutherland<\/strong><span>\u00a0<\/span>\u2013 PhD student\r\n\r\nI am originally from Motherwell, North Lanarkshire however I completed my undergraduate studies at Heriot-Watt University in Edinburgh. During my degree, I was given the opportunity to work within an industrial environment with MOF Technologies Ltd, Belfast (2017-2018). I graduated from Heriot-Watt in 2019 with an MSci in Chemistry with Industrial Experience. I have since started my postgraduate studies at the University of St Andrews with Dr Clarissa M. Czekster on a PhD project entitled \u201c<i>Exploiting cyclic dipeptides as novel anti-cancer therapeutics\u201d<\/i>\r\n\r\nOrcid: <a href=\"https:\/\/orcid.org\/0000-0001-5150-4346\">https:\/\/orcid.org\/0000-0001-5150-4346<\/a>\r\n\r\n&nbsp;\r\n\r\n&nbsp;\r\n\r\n&nbsp;\r\n\r\n<img class=\"wp-image-216 alignright\" src=\"https:\/\/czeksterlab.wp.st-andrews.ac.uk\/files\/2021\/02\/Martha_Simpson-1024x1024.jpg\" sizes=\"(max-width: 256px) 100vw, 256px\" srcset=\"https:\/\/czeksterlab.wp.st-andrews.ac.uk\/files\/2021\/02\/Martha_Simpson-1024x1024.jpg 1024w, https:\/\/czeksterlab.wp.st-andrews.ac.uk\/files\/2021\/02\/Martha_Simpson-300x300.jpg 300w, https:\/\/czeksterlab.wp.st-andrews.ac.uk\/files\/2021\/02\/Martha_Simpson-150x150.jpg 150w, https:\/\/czeksterlab.wp.st-andrews.ac.uk\/files\/2021\/02\/Martha_Simpson-768x769.jpg 768w, https:\/\/czeksterlab.wp.st-andrews.ac.uk\/files\/2021\/02\/Martha_Simpson-1534x1536.jpg 1534w, https:\/\/czeksterlab.wp.st-andrews.ac.uk\/files\/2021\/02\/Martha_Simpson-620x621.jpg 620w, https:\/\/czeksterlab.wp.st-andrews.ac.uk\/files\/2021\/02\/Martha_Simpson.jpg 2013w\" alt=\"\" width=\"256\" height=\"256\" \/>\r\n\r\n<strong>Martha Simpson<\/strong><span>\u00a0<\/span>\u2013 PhD student\r\n\r\nI am originally from Northampton in the East Midlands but moved to York in 2015 to begin my undergraduate studies in Biochemistry. As part of my degree, I undertook a year in industry at Allergan Biologics in Liverpool, where I used LC-MS to characterise antibody-based therapeutics. I (virtually) graduated from the University of York in 2020 with an MBiochem integrated masters. I have since moved to St Andrews to carry out a PhD project under the supervision of Dr Clarissa M. Czekster. My project will involve characterising bacterial and mammalian proteins which are involved in regulating protein degradation as part of the N-end rule.\r\n\r\n&nbsp;\r\n\r\n&nbsp;\r\n\r\n&nbsp;\r\n\r\n<strong><img class=\"alignleft wp-image-265\" src=\"https:\/\/czeksterlab.wp.st-andrews.ac.uk\/files\/2021\/10\/trinh-1024x768.jpg\" sizes=\"(max-width: 284px) 100vw, 284px\" srcset=\"https:\/\/czeksterlab.wp.st-andrews.ac.uk\/files\/2021\/10\/trinh-1024x768.jpg 1024w, https:\/\/czeksterlab.wp.st-andrews.ac.uk\/files\/2021\/10\/trinh-300x225.jpg 300w, https:\/\/czeksterlab.wp.st-andrews.ac.uk\/files\/2021\/10\/trinh-768x576.jpg 768w, https:\/\/czeksterlab.wp.st-andrews.ac.uk\/files\/2021\/10\/trinh-1536x1152.jpg 1536w, https:\/\/czeksterlab.wp.st-andrews.ac.uk\/files\/2021\/10\/trinh-2048x1536.jpg 2048w\" alt=\"\" width=\"284\" height=\"213\" \/>Ng\u1ecdc Anh Th\u01b0 Tr\u1ecbnh<\/strong><span>\u00a0<\/span>\u2013 PhD student\r\n\r\nI am from Viet Nam, where I completed my Bachelor\u2019s degree in Biochemistry at Vietnam National University Ho Chi Minh City (International University) in 2018. Following that, I obtained my Master of Science degree at Newcastle University in 2020 with a graduate thesis on the effect of one-time Ciclosporin A application on adaptive immunity in patients with acute myocardial infarction. In 2021, I started my PhD at the University of St Andrews under the supervision of Dr Clarissa M. Czekster. The objective of my project is to determine the molecular requirements for the activation of various anticancer compounds developed by ProTides technology. Out of research, I also enjoy photography, travelling, and reading.","publications":"[publications flag='individual' code='cmc27' dois='1' max='10' categorise='1']","research_projects":"<ul>\r\n \t<li><span>Antibiofilm peptides<\/span><\/li>\r\n \t<li><span>Environmental microbes and antimicrobial resistance<\/span><\/li>\r\n \t<li><span>Chemical biology to produce novel cyclic peptides<\/span><\/li>\r\n \t<li><span>Protein degradation and recycling in bacteria<\/span><\/li>\r\n \t<li><span>Mechanism of activation of nucleoside products<\/span><\/li>\r\n \t<li><span>Biocatalysis<\/span><\/li>\r\n<\/ul>","related_theme":[119,203,93],"related_centre":77,"contact":"<header class=\"entry-header\" aria-label=\"Content\">\r\n<p class=\"entry-title\">cmc27@st-andrews.ac.uk<\/p>\r\n\r\n<\/header>\r\n<div class=\"entry-content\">\r\n<div>Biomedical Sciences Research Complex<\/div>\r\n<div class=\"place-name\">School of Biology<\/div>\r\n<div class=\"address\">University of St Andrews<\/div>\r\n<div class=\"address\">North Haugh, St Andrews KY16 9ST<\/div>\r\n<\/div>","ID":165,"post_title":"Czekster Lab","post_content":"<img class=\"alignleft size-medium wp-image-215\" src=\"https:\/\/biology.st-andrews.ac.uk\/research\/wp-content\/uploads\/sites\/17\/2022\/12\/TOC-figure-03_Clarissa-Melo-Czekst-300x119.png\" alt=\"\" width=\"300\" height=\"119\" \/>\r\n\r\nWe have around 10<sup>13<\/sup><span>\u00a0<\/span>bacteria living in our bodies, a number comparable to the amount of human cells we possess.\u00a0This community of bacteria inhabiting us is called the microbiota. The human microbiota can contribute to development, outcome and response to treatment of various diseases including cancer, bacterial and viral infections.\r\n\r\nWhy do some bacteria cause disease and can \u201ctake over\u201d environments that they wouldn\u2019t normally occupy? How can we keep good bacteria around and get rid or control the problematic ones?\r\n\r\nOur research combines enzymology, structural biology, chemical biology and microbiology to understand how bacteria produce and use cyclic peptides in interspecies and interkingdom warfare and\/or cooperation. Our purpose is to generate novel drugs, probes, carriers, and technologies that will allow us to control and modulate bacterial populations.\r\n\r\nOur group website: https:\/\/czeksterlab.wp.st-andrews.ac.uk\/\r\n\r\n<img class=\"alignleft size-medium wp-image-216\" src=\"https:\/\/biology.st-andrews.ac.uk\/research\/wp-content\/uploads\/sites\/17\/2022\/12\/Live-dead-example2-01_Clarissa-Melo-Czekst-300x104.png\" alt=\"\" width=\"300\" height=\"104\" \/>","post_excerpt":"Our research combines enzymology, structural biology, chemical biology and microbiology to understand how bacteria produce and use cyclic peptides in interspecies and interkingdom warfare and\/or cooperation. Our purpose is to generate novel drugs, probes, carriers, and technologies that will allow us to control and modulate bacterial populations.","post_author":"68","post_date":"2022-09-08 09:19:58","post_date_gmt":"2022-09-08 08:19:58","post_status":"publish","comment_status":"closed","ping_status":"closed","post_password":"","post_name":"czekster-lab","to_ping":"","pinged":"","post_modified":"2022-12-21 10:18:36","post_modified_gmt":"2022-12-21 10:18:36","post_content_filtered":"","post_parent":0,"guid":"https:\/\/biology.st-andrews.ac.uk\/research\/?post_type=research_group&#038;p=165","menu_order":0,"post_type":"research_group","post_mime_type":"","comment_count":"0","comments":false,"_thumbnail_id":["166","4","2022-09-08 09:19:54","2022-09-08 08:19:54","","CMC-photo-300x225","","inherit","open","closed","","cmc-photo-300x225","","","2022-09-08 09:19:54","2022-09-08 08:19:54","","165","https:\/\/biology.st-andrews.ac.uk\/research\/wp-content\/uploads\/sites\/17\/2022\/09\/CMC-photo-300x225-1.jpg","0","attachment","image\/jpeg","0","166"],"id":165},{"group_members":"<a href=\"mailto:sam31@st-and.ac.uk\" target=\"_blank\" rel=\"noreferrer noopener\">Stuart MacNeill<\/a>\r\nGroup leader\r\n\r\n<a href=\"mailto:liyuan@liyuan\">Liyuan Chen<\/a>\r\nPhD student, 2024-2028\r\n\r\n<a href=\"http:\/\/keenan@keenan\/\">Keenan Parker<\/a>\r\nMSc(Res) student, 2025-2026\r\n\r\n<a href=\"http:\/\/jenna@jenna\/\">Jenna Brown<\/a>\r\nMBiol project student, 2025-2026\r\n\r\n<a href=\"mailto:alice@alice\">Alice Zhen<\/a>\r\nHonours project student, 2025-2026\r\n\r\n<a href=\"http:\/\/ellice@ellice\/\">Ellice McKay<\/a>\r\nHonours project student, 2025-2026","publications":"[publications flag='individual' code='sam31' dois='1' max='100' categorise='1']","research_projects":"<header class=\"entry-header\" aria-label=\"Content\">Chromosomal DNA replication requires the complex interplay of a large number of essential and non-essential protein factors in a temporally- and spatially-coordinated manner. Determining how these factors act together to replicate the genome is central to understanding how the integrity of the genome is maintained within, and across, generations and how genetic diseases such as cancer in humans are avoided. The components of the replication machinery are also potential targets for anti-proliferative drugs and can be used as diagnostic markers for the proliferative state.\r\n\r\nThe complexity of the replication machinery favours the use of simple model systems to dissect problems of protein structure, function and regulation. Indeed, much of what we know about the eukaryotic replication apparatus has come from model system studies. In the MacNeill lab, research is primarily focused on dissecting the molecular biology of<span class=\"style3\">\u00a0chromosomal DNA replication and genome stability\u00a0<\/span>using two contrasting genetically-tractable model systems, the eukaryotic fission yeast\u00a0<strong><span class=\"style1\">Schizosaccharomyces pombe<\/span><\/strong>\u00a0and the halophilic archaeon\u00a0<strong><span class=\"style2\">Haloferax volcanii<\/span><\/strong>. In addition to this, we also study the molecular biology of <strong>T5-like bacteriophages (Demerecviridae)<\/strong>, DNA ligase enzymes encoded by diverse bacteriophages and viruses, and carbohydrate-processing enzymes in haloarchaea. We use a variety of methods to address questions of protein structure and function within the chromosome replication apparatus, including genetics and molecular biology, biochemistry, structural biology and bioinformatics.\r\n<h2 id=\"chromosomal-dna-replication-in-eukaryotes\" class=\"wp-block-heading\">Chromosomal DNA replication in eukaryotes<\/h2>\r\nDNA polymerase delta plays essential roles in eukaryotic chromosomal DNA replication and also in various DNA repair pathways. We are interested in understanding how Pol delta activity in regulated in vivo. Using the fission yeast <strong>Schizosacharomyces pombe<\/strong> as a model system, we are investigating how post-translational modifications affect Pol delta function in vivo, with particular emphasis on modification of the PolD3 and PolD4 subunits of the complex. We have also expressed and purified the four-subunit Pol delta complex from the thermophilic ascomycete fungus\u00a0<strong>Chaetomium thermophilum<\/strong> (Ct) and have determined its structure by cryo-EM in collaboration with Dr\u00a0Ramasubramanian Sundaramoorthy (University of Dundee, work in progress). We have also used X-ray crystallography to obtain an understanding of how <strong>Chaetomium thermophilum<\/strong> PCNA interacts with Ct PolD3, Ct PolD4 and the flap endonuclease Ct Fen1 <a href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/35942639\/\" data-type=\"URL\" data-id=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/35942639\/\">at atomic resolution<\/a> (collaboration with Dr Magnus Alphey, University of St Andrews).\r\n<h2 id=\"chromosomal-dna-replication-and-repair-in-archaea\" class=\"wp-block-heading\">Chromosomal DNA replication and repair in archaea<\/h2>\r\nArchaea constitute the third domain of life on Earth, comprise an estimated 20% of the planet\u2019s biomass and make major impacts on both biosphere and atmosphere.\u00a0We are interested in understanding the enzymes and mechanisms of chromosomal DNA replication and repair in archaeal cells and in what this can tell us about the fundamental processes underlying the maintenance of genetic integrity in all cells. We use the highly tractable halophilic (salt-loving) archaeal organisms\u00a0<strong>Haloferax volcanii<\/strong>\u00a0and <strong>Haloarcula hispanica<\/strong> as model systems as this provides us with a range of molecular genetic tools for functional analysis in vivo. Previously we have studied <a href=\"https:\/\/www.ncbi.nlm.nih.gov\/pubmed\/21976728\">single-stranded DNA binding proteins<\/a>, the <a href=\"https:\/\/www.ncbi.nlm.nih.gov\/pubmed\/19770505\">sliding clamp PCNA<\/a>, <a href=\"https:\/\/www.ncbi.nlm.nih.gov\/pubmed\/16420348\">ATP- and NAD-dependent DNA ligases<\/a>, <a href=\"https:\/\/www.ncbi.nlm.nih.gov\/pubmed\/24723920\">MCM helicase<\/a> and an entirely <a href=\"https:\/\/www.ncbi.nlm.nih.gov\/pubmed\/26337406\">novel DNA repair factor<\/a> named NreA. We are currently investigating the cellular functions of the four <strong>Haloferax volcanii\u00a0<\/strong><a href=\"https:\/\/portlandpress.com\/emergtoplifesci\/article-abstract\/2\/4\/493\/77088\/The-archaeal-RecJ-like-proteins-nucleases-and-ex?redirectedFrom=PDF\">RecJ-like proteins<\/a> to\u00a0gain fundamental insights into how these proteins have evolved to safeguard the integrity of the archaeal genome.\r\n<h2 id=\"molecular-biology-of-bacteriophage-t5-replication\" class=\"wp-block-heading\">Molecular biology of bacteriophage T5 replication<\/h2>\r\nThe T5-like bacteriophages (<strong>Demerecviridae<\/strong>) are a family of lytic bacteriophages that infect Gram-negative bacteria. The phage particles consist of an icosahedral capsid, a lengthy non-contractile tail and a double-stranded DNA genome with the capacity to encode ~160-180 proteins. A number of these proteins have been identified as being essential for phage DNA replication including a DNA polymerase, primase, DNA ligase and exonuclease. We are interested in understanding the function of the remaining essential proteins and understanding how these interact with one another to facilitate rapid replication of the phage genome during infection. We are characterising individual phage T5 proteins biochemically while at the same time using CRISPR\/Cas genome editing methods to allow us to investigate in vivo function in greater detail. One key target is the DNA ligase encoded by T5-like phages. We have solved the structure of this enzyme (from phage vB_PreS_PR1 DNA, a collaboration with structural biologist Dr Julia Richardson, University of Edinburgh), revealing novel features of DNA ligase biology.\r\n<h2 id=\"dna-ligases-for-biotech-applications\" class=\"wp-block-heading\">DNA ligases for biotech applications<\/h2>\r\n<strong>DNA ligases<\/strong> are essential enzymes in all forms of life and are a cornerstone of recombinant DNA technology. The market leader New England Biolabs alone markets six different ligases in <a href=\"https:\/\/international.neb.com\/tools-and-resources\/selection-charts\/dna-ligase-selection-chart\">15 different formulations<\/a>. In this project, we are exploring the outer limits of DNA ligase sequence space to identify novel enzymes with enhanced properties with commercial potential.\u00a0Building on <a href=\"https:\/\/www.ncbi.nlm.nih.gov\/pubmed\/29133882\">recent phylogenetic analysis<\/a>, we are focusing on highly diverged and previously unstudied ATP-dependent ligase enzymes encoded by crAss-like phages present in the human gut, by viruses\u00a0that infect unicellular green algae and\u00a0amoeba, and by early-branching kinetoplastids. Ligase proteins are being expressed and\u00a0purified in recombinant form and the purified enzymes tested for stability and activity on different substrates\u00a0under a range of conditions.\r\n\r\n<\/header>","related_theme":[122,201,200,203],"related_centre":77,"contact":"<span id=\"contact\">Dr Stuart MacNeill<\/span>\r\nSchool of Biology\r\n<a href=\"http:\/\/www.st-andrews.ac.uk\/bsrc\/\">Biomedical Sciences Research Complex<\/a>\r\nUniversity of St Andrews\r\nSt Andrews\r\nKY16 9ST\r\nUK\r\n\r\nT: +44 (0)1334 46 72 68\r\nE: <a href=\"mailto:stuart.macneill@st-andrews.ac.uk\">stuart.macneill@st-andrews.ac.uk<\/a>","ID":154,"post_title":"The MacNeill Lab","post_content":"Research in the MacNeill lab is primarily focused on using molecular genetic tools to probe protein structure, function and regulation in various microbial model systems. In addition to molecular genetic methods, we use biochemistry, structural biology and bioinformatics.\r\n\r\nIn the past our work was focused on dissecting the enzymes and mechanisms of\u00a0DNA replication and genome stability\u00a0in the eukaryotic fission yeast <strong>Schizosaccharomyces pombe<\/strong>\u00a0and the halophilic euryarchaeon\u00a0<strong>Haloferax volcanii<\/strong>. We have also studied the activity of the highly diverged DNA ligase enzymes encoded by\u00a0<strong>crAss-like bacteriophages<\/strong>\u00a0and the function of selected\u00a0carbohydrate-active enzymes (CAZymes) in <strong>haloarchaea<\/strong>. We have also worked on the parasitic protozoan\u00a0<strong>Trypanosoma brucei\u00a0<\/strong>and the non-human infectious kinetoplastid model organism <strong>Crithidia\u00a0fasciculata<\/strong> and have contributed to analysis of the mitosome in <strong>microsporidia<\/strong>.\r\n\r\nPresently, the main focus of the lab is the biology of\u00a0<strong>bacteriophage T5<\/strong>. We are studying the structure and function of the unique split DNA ligase encoded by T5 and the SciA endonuclease responsible for the single-stranded DNA nicks in the packaged phage genome, as well as mechanisms of host cell lysis. Future work will expand the cell lysis work into a broader range of coliphage. In addition to the phage work, we are also completing work on the structure and function of eukaryotic DNA polymerase delta using the thermophilic fungus <strong>Chaetomium thermophilum<\/strong> as a model.\r\n\r\n<span>Click <a href=\"https:\/\/macneill.wp.st-andrews.ac.uk\/\">here<\/a> to visit the lab website.<\/span>","post_excerpt":"Research in the MacNeill lab is primarily focused on using molecular genetic tools to probe protein structure, function and regulation in various microbial model systems. In addition to molecular genetic methods, we use biochemistry, structural biology and bioinformatics.","post_author":"58","post_date":"2022-09-07 23:56:57","post_date_gmt":"2022-09-07 22:56:57","post_status":"publish","comment_status":"closed","ping_status":"closed","post_password":"","post_name":"the-macneill-lab","to_ping":"","pinged":"","post_modified":"2026-03-31 16:22:34","post_modified_gmt":"2026-03-31 15:22:34","post_content_filtered":"","post_parent":0,"guid":"https:\/\/biology.st-andrews.ac.uk\/research\/?post_type=research_group&#038;p=154","menu_order":0,"post_type":"research_group","post_mime_type":"","comment_count":"0","comments":false,"_thumbnail_id":["261","58","2022-12-21 09:58:44","2022-12-21 09:58:44","","MacNeill","","inherit","open","closed","","screenshot-2022-12-21-at-09-58-18","","","2022-12-21 09:59:03","2022-12-21 09:59:03","","154","https:\/\/biology.st-andrews.ac.uk\/research\/wp-content\/uploads\/sites\/17\/2022\/09\/Screenshot-2022-12-21-at-09.58.18.png","0","attachment","image\/png","0","261"],"id":154}],"related_centre":[{"ID":77,"post_title":"Biomedical Sciences Research Complex","post_content":"<span>The\u00a0Biomedical Sciences Research Complex (BSRC) is an interdisciplinary centre for biomedical research with contributions from the Schools of Biology, Chemistry, Medicine, Physics and Astronomy.\u00a0The BSRC's main research themes are infection and immunity, biophysics, molecular medicine, and chemical biology.\u00a0<\/span>\r\n\r\n<a href=\"https:\/\/biology.st-andrews.ac.uk\/bsrc\">Main Website<\/a>","post_excerpt":"","post_author":"4","post_date":"2022-01-17 15:53:50","post_date_gmt":"2022-01-17 15:53:50","post_status":"publish","comment_status":"closed","ping_status":"closed","post_password":"","post_name":"biomedical-sciences-research-complex","to_ping":"","pinged":"","post_modified":"2022-09-20 13:31:47","post_modified_gmt":"2022-09-20 12:31:47","post_content_filtered":"","post_parent":0,"guid":"https:\/\/biology.st-andrews.ac.uk\/research\/?post_type=research_centre&#038;p=77","menu_order":0,"post_type":"research_centre","post_mime_type":"","comment_count":"0","comments":false,"id":77}],"_links":{"self":[{"href":"https:\/\/biology.st-andrews.ac.uk\/research\/wp-json\/wp\/v2\/research_theme\/203","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/biology.st-andrews.ac.uk\/research\/wp-json\/wp\/v2\/research_theme"}],"about":[{"href":"https:\/\/biology.st-andrews.ac.uk\/research\/wp-json\/wp\/v2\/types\/research_theme"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/biology.st-andrews.ac.uk\/research\/wp-json\/wp\/v2\/media\/206"}],"wp:attachment":[{"href":"https:\/\/biology.st-andrews.ac.uk\/research\/wp-json\/wp\/v2\/media?parent=203"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}