{"id":184,"date":"2022-09-08T10:29:31","date_gmt":"2022-09-08T09:29:31","guid":{"rendered":"https:\/\/biology.st-andrews.ac.uk\/research\/?post_type=research_group&p=184"},"modified":"2022-12-21T10:18:53","modified_gmt":"2022-12-21T10:18:53","slug":"da-silva-lab","status":"publish","type":"research_group","link":"https:\/\/biology.st-andrews.ac.uk\/research\/research-group\/da-silva-lab\/","title":{"rendered":"da Silva lab"},"content":{"rendered":"

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Enzymes catalyse virtually all chemical reactions in living organisms, making their rates compatible with life. These proteins have evolved to utilize a range of strategies to achieve incredible rate enhancements in comparison with the corresponding non-catalysed reactions. The study of enzymatic mechanisms is fundamental to elucidate how enzymes work in physical and chemical terms, and how their activity is regulated.<\/p>\n

In the da Silva Lab, we apply techniques of molecular biology, biochemistry, structural biology and physical organic chemistry to unravel the mechanisms of enzymatic reactions catalysed by multi-protein allosteric complexes, tRNA methyltranferases, and nucleotide hydrolases. Particular attention is given to transition-state structure, inhibitor design, and fast protein dynamics.<\/p>\n

We are part of the\u00a0<\/span>Biomedical Sciences Research Complex<\/a>\u00a0<\/span>and the\u00a0<\/span>School of Biology<\/a>\u00a0<\/span>at the\u00a0<\/span>University of St\u00a0Andrews<\/a>. Our lab is located in the BMS Annexe Building on North Haugh.<\/p>\n

Our lab website: https:\/\/dasilva.wp.st-andrews.ac.uk\/<\/p>\n","protected":false},"excerpt":{"rendered":"

In the da Silva Lab, we apply techniques of molecular biology, biochemistry, structural biology and physical organic chemistry to unravel the mechanisms of enzymatic reactions catalysed by multi-protein allosteric complexes, tRNA methyltranferases, and nucleotide hydrolases. Particular attention is given to transition-state structure, inhibitor design, and fast protein dynamics.<\/p>\n","protected":false},"author":69,"featured_media":185,"parent":0,"menu_order":0,"template":"","class_list":["post-184","research_group","type-research_group","status-publish","has-post-thumbnail","hentry"],"jetpack_sharing_enabled":true,"group_members":"

Dr Rafael G da Silva \u2013\u00a0<\/span><\/strong>Principal Investigator<\/em><\/h3>\r\n\"\"I\u2019m a native of Porto Alegre, a city in the south of Brazil. I received a BSc degree in Biology (2002) from Universidade Federal do Rio Grande do Sul, and MSc (2005) and PhD (2008) degrees in Biochemistry from the same university, under the supervision of Dr Luiz Basso. After post-doctoral training (2008-2012) with Dr Vern Schramm at the Albert Einstein College of Medicine in New York, I worked at Pfizer in Connecticut, first as Senior Scientist, then as Principal Scientist (2012-2014). In 2015, I moved to Scotland as a research group leader at the University of St\u00a0Andrews.\r\n

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Dr Suneeta Devi \u2013 Post-doctoral Fellow<\/h3>\r\n\"\"I am from the historical city of Benaras, India. I was fascinated by the abilities of scientific research to alleviate human life throughout my school days, which led me to pursue my undergraduate degree in biology and master\u2019s in biotechnology. My evolving scientific curiosities led me to pursue my PhD with Prof. S Gourinath in structural biology from Jawaharlal Nehru University, New Delhi, India. During my doctoral training, \u00a0I investigated the structure-function relationship of sulfur metabolic enzymes using pathogenic bacteria as a model. Recently, I joined the da Silva lab at the University of St\u00a0Andrews to investigate the underlying mechanism of the human DNPH1 enzyme and to develop biocatalytic routes to isotope-labelled nucleotides, funded by IBioIC.\r\n

<\/h3>\r\n

Gemma Fisher \u2013\u00a0<\/span>Biology (EASTBIO) PhD Student<\/em><\/h3>\r\n\"\"<\/a>I am from Glasgow and completed a BSc in Biochemistry at the University of St\u00a0Andrews. I am now studying towards a PhD in Biology as part of the\u00a0<\/span>EASTBIO Doctoral Training Partnership<\/a>. My research will elucidate the mechanism of\u00a0<\/span>P. arcticus<\/em>\u00a0<\/span>ATP phosphoribosyltransferase with the aim to generate opportunities for protein engineering.\r\n\r\n \r\n\r\n \r\n\r\n \r\n

Ben Read \u2013\u00a0<\/span>Biology (EASTBIO) PhD Student<\/em><\/h3>\r\n\"\"<\/a>Originally from the south-east of England, I came to the University of St\u00a0Andrews where I completed my BSc in Biochemistry. I have continued at St\u00a0Andrews to undertake a PhD in the da Silva lab as part of the EATBIO Doctoral Training Partnership. My project aims to elucidate the mechanism behind allosteric inhibition\/activation of\u00a0<\/span>Acinetobacter baumannii<\/em>\u00a0<\/span>ATP phosphoribosyltransferase, which has untapped antimicrobial potential.","publications":"[publications flag='individual' code='rgds' dois='1' max='10' categorise='1']","research_projects":"Research\u00a0in our\u00a0group\u00a0concerns the enzymology of\u00a0<\/span>histidine biosynthesis and tRNA methylation.\u00a0<\/span><\/strong>We employ a breadth of strategies and techniques (e.g. gene cloning and expression, site-directed mutagenesis, protein purification, steady-state and pre-steady-state kinetics, isothermal titration calorimetry, differential scanning fluorimetry, mass spectrometry, NMR, isotopic labelling of substrates and enzymes, kinetic and binding isotope effects, density-functional theory calculations, protein crystallography, inhibitor design and synthesis) to elucidate the mechanisms of enzymatic reactions. We harness that information to design specific enzyme inhibitors of promising novel targets for antibiotic and anticancer development.\r\n

ATP phosphoribosyltransferase and phosphoribosyl-ATP pyrophosphohydrolase\/phosphoribosyl-AMP cyclohydrolase\r\n<\/strong><\/span><\/h3>\r\n\"\"<\/a>The biosynthesis of histidine involves some unusual enzymatic reactions. Efforts are focused on the first, second and third steps of the pathway, the hetero-octameric and allosteric ATP phosphoribosyltransferase (ATPPRT) and the bifunctional phosphoribosyl-ATP pyrophosphohydrolase\/phosphoribosyl-AMP cyclohydrolase (HisIE). The long-term goal is to understand the principles that underpin enzyme catalysis and allostery in these systems to enable inhibitor design towards novel antibiotics against\u00a0<\/span>Acinetobacter baumannii<\/em>.\r\n

m1A22-tRNA methyltransferase\r\n<\/strong><\/span><\/h3>\r\n\"\"The enzyme m1A22-tRNA methyltransferase (TrmK) is essential for\u00a0<\/span>Staphylococcus aureus<\/em>\u00a0<\/span>survival but absent in humans. We are elucidating the mechanism and substrate specificity of this enzyme, and developing covanlent inhibitors of TrmK towards novel antibiotics against MRSA. We are also investigating human tRNA methyltransferases involved in resistance to current cancer treatments.\r\n\r\n \r\n\r\n \r\n

<\/h3>\r\n ","related_theme":false,"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}],"contact":"

Join Us<\/h1>\r\nWe are always interested in recruiting enthusiastic and motivated students and post-docs to our group. Specific projects for Ph.D. students or post-docs\u00a0are normally advertised here and on FindAPhD.\r\n\r\nProspective Ph.D. students and post-docs bringing their own fellowships, or who want to apply for a fellowship, and are interested in joining the lab, should email Dr da Silva (rgds@st-andrews.ac.uk) at any time\u00a0to discuss available opportunities.\r\n

PhD Projects:<\/h3>\r\n\r\n
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MSc projects available (https:\/\/synergy.st-andrews.ac.uk\/research\/mscres\/mscres-biomedical-sciences\/<\/a>):<\/div>\r\n<\/div>\r\n<\/div>\r\n<\/div>\r\n<\/div>\r\n<\/div>\r\n<\/div>\r\n<\/div>\r\n