{"id":200,"date":"2022-11-28T11:02:10","date_gmt":"2022-11-28T11:02:10","guid":{"rendered":"https:\/\/biology.st-andrews.ac.uk\/research\/?post_type=research_theme&p=200"},"modified":"2022-11-28T14:31:24","modified_gmt":"2022-11-28T14:31:24","slug":"structural-biology","status":"publish","type":"research_theme","link":"https:\/\/biology.st-andrews.ac.uk\/research\/research-theme\/structural-biology\/","title":{"rendered":"Structural Biology"},"content":{"rendered":"","protected":false},"excerpt":{"rendered":"","protected":false},"featured_media":208,"parent":0,"menu_order":0,"template":"","class_list":["post-200","research_theme","type-research_theme","status-publish","has-post-thumbnail","hentry"],"jetpack_sharing_enabled":true,"related_groups":[{"group_members":"Dr Louise Major<\/span>\r\nDr Farhan Ali<\/span>\r\nDr Michela Cerone<\/span>\r\n\r\nPhD students<\/span>\r\nJagwinder Dhaliwal<\/span>\r\nWilliam Mosedale<\/span>\r\nVeronica Harris<\/span>\r\nRachel Humman<\/span>\r\nNora Von Xylander<\/span>\r\nBerta Fatas<\/span>\r\nNgoc Anh Thu Trinh<\/span>\r\nVytautas Kuodis<\/span>\r\nPeter Black<\/span>\r\n\r\nM(Res)<\/span>\r\nOenone Bodman-Harris<\/span>","publications":"[publications flag='individual' code='tks1' dois='1' max='10' categorise='1']","research_projects":"The Smith group uses their interfacial chemical\/biological expertise to find, validate and exploit differences between protozoan and mammalian metabolism.Smith is a leading international authority on parasite lipid metabolism with important publications in this area. His group have to date validated >24 drug targets, conducted several screening campaigns and have 4 lead compound series, which are progressing through the drug discovery pipeline.<\/span>","related_theme":[202,200,119,95,93],"related_centre":77,"contact":"Prof Terry K. Smith CChem, FRSC; FRSB<\/span>\r\nDirector of the Biomedical Sciences Research Complex<\/span>\r\nUniversity Biological Hazards Adviser<\/span>\r\nDirector of the Cat 3<\/span>\r\nRadiation Safety Officer<\/span>\r\nOffice B3.10<\/span>\r\nBiomedical Sciences Research Complex (BSRC),<\/span>\r\nThe North Haugh,<\/span>\r\nThe University,<\/span>\r\nSt. Andrews,<\/span>\r\nFife Scotland.<\/span>\r\nKY16 9ST.<\/span>\r\nTel; office: 01334-463412<\/span>\r\nEmail: tks1@st-andrews.ac.uk<\/span>","ID":239,"post_title":"TKS","post_content":"\"\"\r\n\r\n \r\n\r\nProf Terry Smith is an expert in phospholipid metabolism and the use of mass spectrometry techniques and heads the Lipidomics Facility with GC-MSs and ABSciex 4000 QTrap for lipidomic and focussed metabolomics. Smith being a joint appointment between Biology and Chemistry also has access to a wide-range of world-class analytical facilities, some of which will be utilised in this proposal, i.e. GC-MS and NMR. Prof Smith has received funding from the Wellcome Trust, SULSA, EU and studentships from BBSRC and MRC. He has more than 27 years\u2019 experience in the molecular and biochemical parasitology arena, including T. brucei, T. cruzi, Leishmania, Toxoplasma and Plasmodium. He has published over 75 papers in the last 10 years, including numerous successful collaborations undertaking lipidomic analyses of various pathogens and numerous models for human diseases.<\/span>","post_excerpt":"Prof Terry Smith is an expert in phospholipid metabolism and the use of mass spectrometry techniques and heads the Lipidomics Facility with GC-MSs and ABSciex 4000 QTrap for lipidomic and focussed metabolomics.","post_author":"87","post_date":"2022-12-12 16:03:48","post_date_gmt":"2022-12-12 16:03:48","post_status":"publish","comment_status":"closed","ping_status":"closed","post_password":"","post_name":"tks","to_ping":"","pinged":"","post_modified":"2022-12-21 10:33:05","post_modified_gmt":"2022-12-21 10:33:05","post_content_filtered":"","post_parent":0,"guid":"https:\/\/biology.st-andrews.ac.uk\/research\/?post_type=research_group&p=239","menu_order":0,"post_type":"research_group","post_mime_type":"","comment_count":"0","comments":false,"_thumbnail_id":["241","4","2022-12-12 16:03:15","2022-12-12 16:03:15","","Terry Smith","","inherit","open","closed","","slide1","","","2022-12-12 16:03:25","2022-12-12 16:03:25","","239","https:\/\/biology.st-andrews.ac.uk\/research\/wp-content\/uploads\/sites\/17\/2022\/12\/Slide1.jpg","0","attachment","image\/jpeg","0","241"],"id":239},{"group_members":"Dr Katrin Ackermann<\/span>\r\nLaura Remmel<\/span>","publications":"[publications flag='individual' code='beb2' dois='1' max='10' categorise='1']","research_projects":"
\r\n
\r\n
\r\n
\r\n
Supramolecular structure predictions validated from sparse experimental data (EPSRC funded)<\/div>\r\n
We are working on various projects contributing long range structural constraints and data on binding affinities to integrative models of biomolecular structure and dynamics underpinning function.<\/div>\r\n<\/div>\r\n<\/div>\r\n<\/div>\r\n<\/div>","related_theme":[94,200],"related_centre":77,"contact":"beb2@st-andrews.ac.uk<\/span>\r\n\r\nOffice 153<\/span>\r\nPurdie Building<\/span>\r\nNorth Haugh<\/span>\r\nSt Andrews<\/span>\r\nUnited Kingdom<\/span>","ID":242,"post_title":"Bela Bode","post_content":"The group's research focusses on using Electron Paramagnetic Resonance (EPR) spectroscopy to study the microscopic structure and dynamics of (bio)molecules and materials.<\/span>\r\n\r\nWhen investigating (bio)molecular structures we often find that the methods available have not been proven to be reliably applicable under the specific circumstances of a given research question. The group embraces the challenge of adapting and implementing EPR methodology to obtain the maximum information content. The ultimate vision is a general approach to determine macromolecular complex structures from EPR data through both long-range interactions between spins and their interactions with their surrounding probing the local chemical environment.<\/span>\r\n\r\nIn a nutshell, EPR detects the magnetism arising from the \u201cspin\u201d, a quantum mechanical property of unpaired electrons. Although electrons are contained in all matter, they are commonly paired, quenching their magnetism. However, some molecules and materials, such as radicals and paramagnetic metal ions, exhibit unpaired electrons. Using EPR, it is possible to study the unpaired electron and its surrounding through its magnetic spin measuring distances on the nanometre (one billionth of a metre) scale. Over the past 15 years, these distance measurements have developed into an important and powerful method for investigating the nanoworld of large (bio)molecules.<\/span>\r\n\r\nhttp:\/\/chemistry.st-andrews.ac.uk\/staff\/beb\/group\/index.php<\/span><\/a>","post_excerpt":"The group's research focusses on using Electron Paramagnetic Resonance (EPR) spectroscopy to study the microscopic structure and dynamics of (bio)molecules and materials.","post_author":"85","post_date":"2022-12-12 16:12:20","post_date_gmt":"2022-12-12 16:12:20","post_status":"publish","comment_status":"closed","ping_status":"closed","post_password":"","post_name":"bela-bode","to_ping":"","pinged":"","post_modified":"2022-12-21 10:16:57","post_modified_gmt":"2022-12-21 10:16:57","post_content_filtered":"","post_parent":0,"guid":"https:\/\/biology.st-andrews.ac.uk\/research\/?post_type=research_group&p=242","menu_order":0,"post_type":"research_group","post_mime_type":"","comment_count":"0","comments":false,"_thumbnail_id":["243","4","2022-12-12 16:12:12","2022-12-12 16:12:12","","Bela Bode_Bela Bode","","inherit","open","closed","","bela-bode_bela-bode","","","2022-12-12 16:12:12","2022-12-12 16:12:12","","242","https:\/\/biology.st-andrews.ac.uk\/research\/wp-content\/uploads\/sites\/17\/2022\/12\/Bela-Bode_Bela-Bode.jpg","0","attachment","image\/jpeg","0","243"],"id":242},{"group_members":"Stuart MacNeill<\/a>\r\nGroup leader\r\n\r\nLiyuan Chen<\/a>\r\nPhD student, 2024-2028\r\n\r\nKeenan Parker<\/a>\r\nMSc(Res) student, 2025-2026\r\n\r\nJenna Brown<\/a>\r\nMBiol project student, 2025-2026\r\n\r\nAlice Zhen<\/a>\r\nHonours project student, 2025-2026\r\n\r\nEllice McKay<\/a>\r\nHonours project student, 2025-2026","publications":"[publications flag='individual' code='sam31' dois='1' max='100' categorise='1']","research_projects":"
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\u00a0chromosomal DNA replication and genome stability\u00a0<\/span>using two contrasting genetically-tractable model systems, the eukaryotic fission yeast\u00a0Schizosaccharomyces pombe<\/span><\/strong>\u00a0and the halophilic archaeon\u00a0Haloferax volcanii<\/span><\/strong>. In addition to this, we also study the molecular biology of 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

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 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\u00a0Chaetomium 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 Chaetomium thermophilum<\/strong> PCNA interacts with Ct PolD3, Ct PolD4 and the flap endonuclease Ct Fen1 at atomic resolution<\/a> (collaboration with Dr Magnus Alphey, University of St Andrews).\r\n

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\u00a0Haloferax volcanii<\/strong>\u00a0and 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 single-stranded DNA binding proteins<\/a>, the sliding clamp PCNA<\/a>, ATP- and NAD-dependent DNA ligases<\/a>, MCM helicase<\/a> and an entirely novel DNA repair factor<\/a> named NreA. We are currently investigating the cellular functions of the four Haloferax volcanii\u00a0<\/strong>RecJ-like proteins<\/a> to\u00a0gain fundamental insights into how these proteins have evolved to safeguard the integrity of the archaeal genome.\r\n

Molecular biology of bacteriophage T5 replication<\/h2>\r\nThe T5-like bacteriophages (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

DNA ligases for biotech applications<\/h2>\r\nDNA 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 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 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":"Dr Stuart MacNeill<\/span>\r\nSchool of Biology\r\nBiomedical 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: 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 Schizosaccharomyces pombe<\/strong>\u00a0and the halophilic euryarchaeon\u00a0Haloferax volcanii<\/strong>. We have also studied the activity of the highly diverged DNA ligase enzymes encoded by\u00a0crAss-like bacteriophages<\/strong>\u00a0and the function of selected\u00a0carbohydrate-active enzymes (CAZymes) in haloarchaea<\/strong>. We have also worked on the parasitic protozoan\u00a0Trypanosoma brucei\u00a0<\/strong>and the non-human infectious kinetoplastid model organism Crithidia\u00a0fasciculata<\/strong> and have contributed to analysis of the mitosome in microsporidia<\/strong>.\r\n\r\nPresently, the main focus of the lab is the biology of\u00a0bacteriophage 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 Chaetomium thermophilum<\/strong> as a model.\r\n\r\nClick 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&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":"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\nMain 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&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\/200","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\/208"}],"wp:attachment":[{"href":"https:\/\/biology.st-andrews.ac.uk\/research\/wp-json\/wp\/v2\/media?parent=200"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}