MSc (Res) in Biology: Biomedical Sciences
The MSc(Res) in Biology degree in the biomedical sciences is a 12-month, research-only degree, in which you will undertake a supervised research project in the area of biomedical sciences.
You will be based in the interdisciplinary Biomedical Sciences Research Complex (BSRC), based at the North Haugh science campus in St Andrews.
The MSc (Res) is examined by a 30,000-word research thesis.
Skills training
In addition to the project-specific training that you will receive during your degree, MSc (Res) students will also have access to a wide range of training in transferable skills through the University's GRADskills programme.
Specific postgraduate programmes run within the School of Biology may also offer additional training, for instance in statistical, bioinformatics or molecular techniques.
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You may apply for placement in advertised projects (see the list of current projects further on this page) or contact potential supervisors directly.
Potential candidates are recommended to contact a potential supervisor before applying. If you are self-funded and interested in working with a supervisor who does not currently have a project listed, please contact that person directly.
Biology has two dates for admission to this degree: September and January each year.
If you would like to make a formal application to study for an MSc (Res) at St Andrews, please complete an application using the online system.
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You should have an undergraduate Honours degree at 2.1 level or better in a relevant discipline (for example, biochemistry, molecular biology, biomedicine, biomolecular sciences, microbiology, virology, or chemistry). Students from backgrounds such as mathematics and physics may be accepted under exceptional circumstances.
If you studied for your first degree outside of the UK, please see the international entry requirements.
For non-native English speakers, please see the English language requirements.
Applicants will be short-listed by the project supervisor. Short-listed applicants will be interviewed by members of the School of Biology Postgraduate Recruitment Committee and/or other academic staff, with successful performance at interview being a requirement for entry onto the degree.
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For postgraduate tuition fees for Biology MSc (Res) programmes, please see the University's research tuition fees page.
Scholarships, research council funding or other arrangements may be available for this programme. See the scholarships page for more information.
Research projects
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Supervisor: Dr Carlos Penedo
Single-stranded DNA binding proteins (SSB) are ubiquitous across all organisms and they play key roles in genome maintenance by protecting single-stranded nucleic acids from damage. SSBs are characterised by the presence of an OB-fold (oligonucleotide/oligopeptide/oligosaccharide) binding motif to recognise single-strand DNA.
The Penedo lab has characterised an archaeal single-stranded DNA binding protein and demonstrated its monomeric character, its cooperative mode of action and, strikingly, its ability to efficiently bind RNA.
In this project, you will explore potential applications of this protein using synthetic biology and biophysical approaches including cutting edge single-molecule microscopy.
Relevant references
- Morten, Michael et al. 2017. “High-Affinity RNA Binding by a Hyperthermophilic Single-Stranded DNA-Binding Protein.” Extremophiles, January. doi:10.1007/s00792-016-0910-2.
- Morten, M. J., et al “Binding Dynamics of a Monomeric SSB Protein to DNA: A Single-Molecule Multi-Process Approach.” Nucleic Acids Research, November. doi:10.1093/nar/gkv1225.
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Supervisor: Dr Judith Sleeman
The main theme of research in Sleeman's group is the cellular organisation of RNA biology. Their work has implications for the fundamental understanding of how cells work and is also of major significance for understanding degenerative human diseases including Spinal Muscular Atrophy (an inherited neurodegenerative condition) and Myotonic Dystrophy Type 1 (an inherited condition with variable symptoms including muscle weakness and myotonia).
The group's key expertise lies in mammalian cell culture and microscopy, including live cell microscopy. Together with key collaborators in the UK, Canada and Australia, the group combines this with proteomics, electron microscopy, lipidomics and anatomy.
Relevant references
- Neurochondrin interacts with the SMN protein suggesting a novel mechanism for Spinal Muscular Atrophy pathology. Thompson LW, Morrison KD, Shirran SL, Groen EJN, Gillingwater TH, Botting CH, Sleeman JE. J Cell Sci. 2018 Mar 5. pii: jcs.211482. doi: 10.1242/jcs.211482.
- Transcriptionally-correlated sub-cellular dynamics of MBNL1 during lens development and their implication for the molecular pathology of Myotonic Dystrophy type I. Stewart M. Coleman, Alan R. Prescott, Judith E. Sleeman. Biochem. J. 458:817-27.
- Time-resolved quantitative proteomics implicates the core snRNP protein, SmB, in neural trafficking. Alan R Prescott, Alexandra Bales, John James, Laura Trinkle-Mulcahy and Judith E. Sleeman. (2014) J Cell Sci. 127:812-827.
- Sleeman J.E., Trinkle-Mulcahy L. (2014) Nuclear bodies: new insights into assembly/dynamics and disease relevance. Curr Opin Cell Biol. Apr 3;28C:76-83. doi: 10.1016/j.ceb.2014.03.004.
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Supervisor: Dr Jens Tilsner
Membrane contact sites are cellular communication hubs at the interfaces of different organelles, where two membranes are held in very close (less than 30 nm) proximity to allow the direct exchange of lipids, calcium and other signalling molecules. Tethering proteins span both membranes and establish and regulate the contact sites. In plants, one unique type of membrane contact sites exists at nano-channels connecting all plant cells across the cell wall. The plasma membrane and endoplasmic reticulum membranes are both continuous between cells through these channels.
This project will characterise the recently discovered putative tethering protein that links the two membranes and likely controls plant cell-cell-communication during development and disease.
Relevant references
- Tilsner et al. (2016) Staying tight: plasmodesmal membrane contact sites and the control of cell-to-cell connectivity in plants. Annual Review of Plant Biology 67: 337-364. doi:10.1146/annurev-arplant-043015-111840
- Perez-Sancho et al. (2016) Stitching organelles: organization and function of specialized membrane contact sites in plants. Trends in Cell Biology 26: 705-717. doi:10.1016/j.tcb.2016.05.007
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Supervisor: Dr Rafael Guimaraes da Silva
Enzymatic reaction rates increase exponentially with temperature. Nonetheless, cold-adapted enzymes have a very high catalytic rate at low temperature in comparison with their warm-adapted counterparts. How do these enzymes work? Can we engineer cold-adapted enzymes for biotechnological purposes? Dissecting the chemistry going on within the active sites of enzymes can pave the way for rational engineering of desirable catalytic properties.
Students will acquire proficiency in:
- protein expression and purification
- enzyme kinetics
- crystallography
- site-directed mutagenesis
- enzymatic synthesis
- purification of isotope-labelled molecules.
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Supervisor: Dr Carlos Penedo
Super-resolution imaging techniques are revolutionising our understanding of biological processes. However, their widespread application to resolve duplex nucleic acid structures (dsNA) from single-stranded regions (ssNA) remains a challenge.
In this project, you will aim to break this limitation by developing an imaging method for NA sequences based on the use of single-stranded binding (SSB) proteins as staining agents to obtain high-resolution structural details of nucleic acid sequences as never seen before.
Relevant references
- D. Baddeley, J. Bewersdorf. Biological insight from super-resolution microscopy: What can we learn from localization-based images. Ann. Rev. Biochem. 89: 965-989 (2017)
- Morten et al. Binding dynamics of a monomeric SSB protein to DNA: a single-molecule multi-process approach. Nucleic Acids Res. 43: 10907-10924 (2015)
- Morten et al. High-affinity RNA binding by a hyperthermophilic single-stranded DNA-binding protein. Extremophiles, 21:369-379 (2017)
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Supervisor: Dr Clarissa Czekster
Bacteria use small peptides to communicate and to compete and cooperate with other bacteria and with their hosts (us). The Czekster group is interested in manipulating the enzymes that make these molecules so we can produce novel compounds to be tested as anticancer and antimicrobial drugs.
The project combines molecular, synthetic, chemical and structural biology (x-ray crystallography), thermodynamics and activity assays to determine how we can expand the substrate scope of different classes of enzymes involved in the production of these small peptides.
For more specific details about projects in the group, please contact Clarissa Czekster (cmc27@st-andrews.ac.uk).
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Supervisor: Dr Stuart MacNeill
In all forms of life, successful chromosomal DNA replication is essential for maintaining genome integrity. Defective replication impacts genome structure and information content in a variety of ways, including sequence deletion, insertion and duplication, point mutation and
chromosome fusion. Research in the MacNeill Lab is focused on understanding molecular mechanisms of eukaryotic genome stability at the molecular level, using the fission yeast Schizosaccharomyces pombe and the thermophilic ascomycete fungal species Chaetomium thermophilum as model
systems for molecular genetic and structural studies, respectively. An MSc(Res) project in this area will allow you to gain vital experience in a wide variety of techniques encompassing cell biology, genetics, molecular biology and biochemistry, providing excellent preparation for future PhD studies in genome stability.
For more information, see the MacNeill Lab website.
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Supervisor: Dr David Ferrier
Dr Ferrier's project seeks to understand how the diversity of animal forms have evolved via changes to their development, usually taking the homeobox genes of the Hox/ParaHox and related clusters as a starting point.
The project studies a variety of invertebrate species (including amphioxus, Ciona, annelids, arthropods, cnidarians and sponges), with the aim of focusing on major transitions in animal evolution, including the origins of the animal kingdom, the origin of the bilaterally symmetrical animals (bilaterians) and the origin of chordates and vertebrates.
Relevant references
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Supervisor: Dr Ildiko Somorjai
Have you ever wondered why some animals regenerate well, and humans do not? Are you interested in how new genes are born, and what generates diversity in animal body forms? The Somorjai Lab addresses these problems from evolutionary, developmental and cell biological perspectives.
The lab predominantly uses the marine invertebrate chordate “amphioxus” due to its genetic and anatomical similarly to simple vertebrates. They also work on flatworms, which have amazing regenerative powers and multipotent stem cells.
The project will depend on the student’s interests and background, but could include:
- gene expression analyses
- embryology
- immunohistochemistry
- confocal microscopy
- genomics
- phylogenetic analyses.
Find out more about the Somorjai Lab.
Relevant references
- Bertrand S, Escriva H. Evolutionary crossroads in developmental biology: amphioxus. Development. 2011 Nov;138(22):4819-30.
- Somorjai IM, Somorjai RL, Garcia-Fernàndez J, Escrivà H. Vertebrate-like regeneration in the invertebrate chordate amphioxus. Proc Natl Acad Sci U S A. 2012 109(2):517-22.
- Dailey, SC, Planas, RF, Espier, AR, Garcia-Fernandez, J and Somorjai, IML Asymmetric distribution of pl10 and bruno2, new members of a conserved core of early germline determinants in cephalochordates. Frontiers in Ecology and Evolution. 2016. 3, 156.
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Supervisor: Dr Stuart MacNeill
Highly-efficient chromosomal DNA replication is essential for all forms of life. The archaeal replication machinery represents a simplified version of that found in eukaryotic cells but exhibits a number of intriguing features that shed light on how eukaryotic replication evolved.
Our research has focused on using the genetically tractable haloarchaeal organisms Haloferax volcanii and Haloarcula hispanica as models for dissecting archaeal DNA replication. This MSc (Res) project will allow you to learn how to genetically manipulate Haloferax volcanii and/or Haloarcula hispanica to explore molecular mechanisms of chromosome replication in these organisms. To complement these studies, you will also undertake biochemical or
structural investigation analysis of one or more archaeal replication factors. For more information, see the MacNeill Lab website.
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Supervisor: Dr Carlos Penedo
Antibiotic resistance is becoming a global threat to human life that causes an increasing number of deaths per year.
In this project, you will investigate bacterial gene regulation pathways that involve exclusively mRNA sequences. These mRNA structures, so-called riboswitches, regulate the expression of crucial genes in response to small metabolites including nucleic acids, aminoacids and vitamins. Importantly, riboswitches are widespread in bacteria and archaea but almost absent in higher organisms, so they are becoming increasingly interesting as antibiotic targets.
In this project, you will explore some recently discovered riboswitches and their potential in synthetic biology and as antibiotic targets.
Relevant references
- Mehdizadeh Aghdam E, Hejazi MS, Barzegar A. Riboswitches: from living biosensors to novel targets of antibiotics, Gene 2016, 592, 244-59
- Heppell, B., Blouin, S., Dussault, A.-M., Mulhbacher, J., Ennifar, E., Penedo, J.C., and Lafontaine, D.A. Molecular insights into the ligand-controlled organization of the SAM-I riboswitch. (2011) Nature Chemical Biology 7, 384–392.
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Supervisor: Dr Stuart MacNeill
Bacteriophage T5 is a model E. coli-infecting lytic phage with a 121 kb linear double-stranded DNA genome that is arranged into pre-early, early and late transcription units, encoding in total around 160 proteins and 20-25 tRNAs. The genomes of over 100 T5-like bacteriophages
have now been sequenced – these display a high level of genetic synteny, highlighting the importance of this conserved genetic organisation for successful phage infection. We have recently developed efficient methods for editing the T5 genome. This has allowed us to delete non-essential genes from the genome, and to insert non-T5 genes into the genome, but at all times respecting the pre-existing genetic organisation. An MSc(Res) project in this area will exploit the genome editing tools to ask wider questions about the genetic structure of T5, in order to gain an understanding of the importance of genetic organisation in the T5 life cycle. Issues to be addressed will include the importance of
transcription unit orientation, gene order within transcription units, and temporal expression, for successful infection. Techniques to be used will include molecular biology, microbiology and biochemistry. For more information, see the MacNeill lab website.
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Supervisor: Dr Peter Coote
Use an invertebrate model (Galleria mellonella – wax-moth larvae) to study bacterial and fungal infections in vivo:
- Determine the efficacy of drug treatments versus human pathogens in vivo, eg. Mycobacterium, multi-drug resistant (MDR) Gram –ves such as Pseudomonas aeruginosa.
- Identify novel, synergistic, combination treatments in vivo. Combinations can involve ‘repurposed’ drugs, efflux pump inhibitors, additional antibiotics etc.
- Study the selection of antibiotic resistance in vivo and characterise the effect of antibiotic resistance on microbial ‘fitness’ and virulence during infection.
- Evaluate the effect in vivo of specific mutations conferring resistance or reducing virulence eg. over-expression or deletion of multi-drug pumps in P. aeruginosa.
Relevant references
- Thanyaluck Siriyong, Supayang P. Voravuthikunchai and Peter J. Coote (2018) Steroidal alkaloids and conessine from the medicinal plant Holarrhena antidysenterica restore antibiotic efficacy in a Galleria mellonella model of multidrug-resistant Pseudomonas aeruginosa infection. BMC Comp. Altern. Med. 18: 285. doi: 10.1186/s12906-018-2348-9.
- Frances M. Entwistle and Peter J. Coote (2018) Evaluation of greater wax moth larvae, Galleria mellonella, as a novel in vivo model for non-tuberculosis Mycobacteria infections and antibiotic treatments. J. Med. Microbiol. doi: 10.1099/jmm.0.000696.
- Miquel Perez Torres, Frances Entwistle & Peter J. Coote (2016) Effective immunosuppression with dexamethasone phosphate in the Galleria mellonella larva infection model resulting in enhanced virulence of Escherichia coli and Klebsiella pneumoniae. Med. Microbiol. & Immunol. 205: 333-343.
- Dougal H. Adamson, Vasare Krikstopaityte and Peter J. Coote (2015) Enhanced efficacy of putative efflux-pump inhibitor/antibiotic combination treatments versus MDR strains of Pseudomonas aeruginosa in a Galleria mellonella in vivo infection model. J. Antimic. Chemother. 70: 2271-2278.
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Supervisor: Dr Michael M Nevels
The presence of DNA outside the nucleus constitutes a danger signal that triggers innate immune activation. However, recent evidence has challenged the view that location is the only factor determining foreign DNA sensing and implies mechanisms distinguishing between ‘self’ and ‘non-self’ nuclear DNA.
The Nevels lab has previously shown that the DNA genome of cytomegalovirus (CMV) is chromatinized differently compared to cellular chromatin. They propose that, rather than recognising viral nuclear DNA alone, the cell may distinguish between viral and cellular chromatin structures.
This project will investigate how CMV chromatin structure is linked to nuclear viral DNA sensing and innate immune signalling.
Relevant references
- Dunphy G, Flannery SM, Almine JF, Connolly DJ, Paulus C, Jønsson KL, Jakobsen MR, Nevels MM, Bowie AG, Unterholzner L (2018). Non-canonical activation of the DNA sensing adaptor STING by ATM and IFI16 mediates NF-κB signalling after nuclear DNA damage. Mol Cell 71(5):745-760.
- Zalckvar E, Paulus C, Tillo D, Asbach-Nitzsche A, Lubling Y, Winterling C, Strieder N, Mücke K, Goodrum F, Segal E, Nevels M (2013). Nucleosome maps of the human cytomegalovirus genome reveal a temporal switch in chromatin organization linked to a major IE protein. Proc Natl Acad Sci USA 110(32):13126-31.
- Mücke K, Paulus C, Bernhardt K, Gerrer K, Schön K, Fink A, Sauer EM, Asbach-Nitzsche A, Harwardt T, Kieninger B, Kremer W, Kalbitzer HR, Nevels M (2014) Human cytomegalovirus major immediate early 1 protein targets host chromosomes by docking to the acidic pocket on the nucleosome surface. J Virol 88(2):1228-48.
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Supervisor: Dr Marcus Bischoff
During morphogenesis, cells undergo various behaviours, such as migration and shape change, which need to be coordinated to shape tissues and organs. How this coordination is achieved is still elusive. The Bischoff lab studies cell behaviours during the formation of the adult abdominal epidermis of Drosophila.
Your MSc (Res) project will employ a combination of in vivo 4D microscopy, cell biology techniques and sophisticated genetics to study cytoskeletal dynamics that underlie the coordination of cell migration and apical constriction. These insights will be of widespread relevance, since the (mis-)regulation of cell behaviour is also fundamental to wound repair and tumour progression.
Relevant references
- Bischoff M and Cseresnyes Z (2009). Cell rearrangements, cell divisions and cell death in a migrating epithelial sheet in the abdomen of Drosophila. Development 136, 2403-2411.
- Bischoff M (2012). Lamellipodia-based migrations of the larval epithelial cells contribute to the closure of the adult abdominal epithelium of Drosophila. Dev Biol 363, 179-190.
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Supervisor: Dr Helder Ferreira
Telomeres are protein-DNA structures that protect the ends of linear chromosomes. Telomeres shorten every time cells replicate. Curiously, although telomeres prevent chromosome ends being recognised as DNA double-strand breaks (DSBs), telomere maintenance requires DNA repair proteins. How short telomeres are differentiated from DSBs is one of the great mysteries of telomere biology. Given that SUMO modification is heavily implicated in both DNA repair and telomere length maintenance, one hypothesis is that sumoylation may help define the appropriate response.
This project, in budding yeast, will involve training in genetic modification as well as protein purification and analysis of mass spectrometry data.
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Supervisor: Professor Malcolm White
Archaea occupy a unique position on the tree of life and are thought to be the progenitors of the eukaryotes. As such, they have many proteins and pathways in common with humans. At the same time, many archaea inhabit extreme environments where DNA damage is very frequent and dangerous.
The White lab is interested in the mechanism archaea use to repair their DNA, particularly the pathways of Nucleotide Excision and Mismatch Repair, where there are some fascinating evolutionary questions.
This project will focus on the molecular biology and genetics of archaeal repair pathways in the model organism Sulfolobus solfataricus.
Relevant references
- DNA repair in the Archaea – an emerging picture White MF and Allers T (2018) FEMS Microbiol Rev 42, 514-526.
- The evolution and mechanisms of Nucleotide Excision Repair proteins Rouillon, C and White MF (2011) Res Microbiol 162, 19-26.
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Supervisor: Dr Clarissa Czekster
Bacteria use small peptides to communicate and to compete and cooperate with other bacteria and with their hosts (us). The Czekster group is interested in understanding how these peptides are made and how we can manipulate bacteria into making molecules of our choosing to be used in our advantage.
The group works with pathogenic bacteria that cause disease by competing with other bacteria to establish infection. Their strategy is interdisciplinary, comprising molecular, synthetic and chemical biology, structural biology (x-ray crystallography), thermodynamics and microbiology.
For more specific details about projects in the group, please contact Clarissa Czekster (cmc27@st-andrews.ac.uk).
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Supervisor: Dr Rafael Guimaraes da Silva
Antimicrobial resistance is on the rise and poses a formidable threat to human and animal health. Exploring novel molecular targets for antibiotic development is of paramount importance towards new drugs.
The da Silva lab employs molecular biology, enzymology, protein chemistry and structural biology to elucidate the reaction mechanism of enzymes essential for survival or virulence of Staphylococcus aureus, but absent in humans, and harnesses this information in rational drug design against S. aureus.
Students will acquire proficiency in protein expression and purification, enzyme kinetics, crystallography, and site-directed mutagenesis.
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Supervisor: Dr Michael Nevels
The human cytomegalovirus (CMV), one of eight human herpesviruses, establishes lifelong infections in the majority of people worldwide. In most of us, CMV infections cause few or no symptoms. However, CMV is a major pathogen in transplant recipients and other immunosuppressed patients, and this virus is the leading cause of birth defects in the UK.
Dr Nevels' lab studies how chromatin-based epigenetic processes in the viral and human genome control CMV replication and persistence. They also investigate the intrinsic and innate immune responses CMV counteracts in its host cells.
This project will explore how the chromatin-associated CMV immediate-early protein 1 (IE1) antagonizes innate immunity, and how these findings may be exploited for innovative antiviral strategies.
Relevant references
- Vasou A, Paulus C, Narloch J, Gage ZO, Rameix-Welti MA, Eléouët JF, Nevels M, Randall RE, Adamson CS. Modular cell-based platform for high throughput identification of compounds that inhibit a viral interferon antagonist of choice (2018). Antiviral Res 150:79-92.
- Harwardt T, Lukas S, Zenger M, Reitberger T, Danzer D, Übner T, Munday DC, Nevels M, Paulus C (2016). Human cytomegalovirus immediate-early 1 protein rewires upstream STAT3 to downstream STAT1 signaling switching an IL6-type to an IFNγ-like response. PLoS Pathog 12(7):e1005748.
- Mücke K, Paulus C, Bernhardt K, Gerrer K, Schön K, Fink A, Sauer EM, Asbach-Nitzsche A, Harwardt T, Kieninger B, Kremer W, Kalbitzer HR, Nevels M (2014) Human cytomegalovirus major immediate early 1 protein targets host chromosomes by docking to the acidic pocket on the nucleosome surface. J Virol 88(2):1228-48.
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Supervisor: Dr David Hughes
The ubiquitin-like protein ISG15 is strongly induced by interferon and is critical for regulating how cells respond to viral infections. Our understanding of ISG15 biology significantly lags behind that of other similar systems, such as ubiquitin and the SUMO pathways. Remarkably, patients have been identified that have a defective ISG15 gene, which has huge implications on our understanding of the interplay between ISG15 and the antiviral response.
Using a range of cutting-edge techniques, projects are available that are aimed at making a significant contribution to our understanding of the ISG15 system and its interplay with innate immunity.
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Supervisor: Professor Terry K Smith
Parasitic protozoa cause neglected tropical diseases that affect millions of people throughout the tropics and sub-tropics. There is an urgent need to identify and develop novel therapeutics that are safe, cheap and readily administered.
Biochemical analysis using a range of stable isotope labelling methods, quantification of metabolites and proteins, various enzymatic assays, numerous cutting edge mass spectrometry methodologies, including lipidomic and metabolomics approaches, help us understand the parasite’s 
requirements for survival and their weakness that we can exploit. Multi-disciplinary, cutting-edge research approaches allow identification and validation of novel drug targets, in conjunction with high-throughput screening to identify novel lead compounds.
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Supervisor: Dr Jens Tilsner
Plant viruses are major crop pathogens and a threat to global food security. Unlike animal viruses, they must overcome the barrier of the plant cell wall in order to spread their infection throughout the host. They do this by moving their genome through nano-channels spanning the cell walls with the aid of virus-encoded transport proteins.
The Tilsner group has discovered that the transport proteins of many important crop viruses are post-translationally modified through the addition of lipid anchors.
This project will use viral reverse genetics, protein biochemistry and live-cell imaging to uncover the role of this post-translational modification in infection.
Relevant references
- Tilsner et al. (2013) Replication and trafficking of a plant virus are coupled at the entrances of plasmodesmata. Journal of Cell Biology 201: 981-995. doi:10.1083/jcb.201304003.
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Supervisor: Dr Carlos Penedo
Bacteria have developed uptake systems to communicate the cytoplasm with the extracellular environment and selectively transfer specific ions between them. These communication channels are commonly composed of several membrane proteins that organise themselves into a pore structure, partially or fully embedded within the cell membrane.
In this project, you will use state-of-the-art single-molecule fluorescence microscopy and bioconjugation techniques in combination with X-ray crystallography and EPR techniques to determine the details of the gating mechanism, the stoichiometry of the macromolecular assembly, the structure of each conformer present in solution and their switching time scale.
Relevant references
- Pliotas, C., Naismith, J. H. Spectator no more, the role of the membrane in regulating ion channel function (2017) Curr. Op. Struct. Bio. 45, 59-66.
- Wang et al. Structural dynamics of potassium-channel gating revealed by single-molecule FRET. (2016) Nat. Struct. Mol. Bio. 23, 31-36.
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Supervisor: Dr Stuart MacNeill
DNA ligases are essential enzymes in all forms of life on Earth and are a cornerstone of recombinant DNA technology.
This MSc(Res) project will explore the properties of highly diverged and previously unstudied ATP-dependent ligase enzymes, with a view to uncovering enzymes with enhanced biochemical properties suitable for biotech applications. Enzymes encoded by diverse
bacteriophages, eukaryotic viruses and cellular organisms will be expressed and purified in recombinant form and tested for stability and activity under a range of conditions and on different substrates. The project will serve as an excellent introduction to recombinant DNA technology, protein expression and purification, and nucleic acid biochemistry, and provide an excellent preparation for future PhD studies. For more information, see the MacNeill lab website.
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Supervisor: Dr Tracey Gloster
Carbohydrates are ubiquitous throughout nature, but, unlike proteins and DNA, a template does not determine their sequence or structure. Instead, the specificity and localisation of the enzymes responsible for their synthesis, degradation and modification have full control over the carbohydrates that exist in nature.
The Gloster group is interested in the structure, mechanism and function of carbohydrate processing enzymes, primarily those from eukaryotes, which are implicated in disease. The group uses a multi-disciplinary approach, involving molecular biology, biochemistry, enzymology, structural biology (X-ray crystallography) and cell biology.
For more specific details about projects in the group, please contact Tracey Gloster (tmg@st-andrews.ac.uk).
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Supervisor: Professor Malcolm White
CRISPR stands for “Clustered Regularly Interspaced Short Palindromic Repeats”. These direct repeats are present in many prokaryotes and provide a defence against invading genetic elements such as viruses.
The White lab is interested in the mechanisms used to capture new viral DNA, which confers immunity, and in the processes used to target and destroy viruses. The lab studies this process both in archaea and in the human pathogen Mycobacterium tuberculosis.
The project will give a good grounding in a wide variety of molecular biology techniques.
Relevant references
- Ring nucleases deactivate type III CRISPR ribonucleases by degrading cyclic oligoadenylate Athukoralage JS, Rouillon C, Graham S, Grüschow S and White MF (2018) Nature 562, 277-280.
- Control of cyclic oligoadenylate synthesis in a type III CRISPR system Rouillon C, Athukoralage JS, Graham S, Grüschow S and White MF (2018) eLife 7:e36734.
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Supervisor: Dr Alan Stewart, School of Medicine
The development of new treatments for neurological disorders such as schizophrenia, Parkinson Disease and Dementia is slow. The most important factor which limits the development of novel CNS-targeted therapeutics is not the identification of new targets (despite this being where the vast majority of research efforts are focused) but the blood-brain barrier (BBB), a network of capillary blood vessels which limits the penetration of most CNS drug candidates. Essentially none of the currently available large-molecule pharmaceutics, including peptides, recombinant proteins, monoclonal antibodies, RNA interference-based drugs and gene therapies, readily cross the BBB. In addition to this, more than 98% of all small molecule therapeutics do not cross the BBB, and the ones that do only treat a handful of CNS conditions.
Albuminoid proteins (which include serum albumin, alpha-fetoprotein, vitamin D binding protein and afamin) are a class of structurally related plasma proteins which act as circulatory transporters. It has been shown that one of these proteins, afamin, has the ability to transport vitamin E across BBB models (Kratzer et al. J. Neurochem. 108: 707-718).
The aim of the project is to examine whether afamin may be recombinantly expressed and engineered such as to allow it to carry pharmaceutics to the CNS.
The project will be supervised by Dr Alan Stewart in the School of Medicine. Dr Stewart’s laboratory is situated in the state-of-the-art Medical and Biological Sciences Building, which is located at the heart of the University’s science campus.
During the project, the student will gain experience in a range of laboratory techniques that include protein expression, purification and biophysical characterisation (for example, isothermal titration calorimetry) as well as endothelial cell culture.
Additionally, training will be provided by Albumedix, a global biopharmaceutical company that specialises in developing albumin-based products and technologies for advanced drug and vaccine formulation, extended drug half-life and improved drug delivery. Over the course of the project, the student may spend some time in Albumedix's Nottingham-based laboratories, thus gaining research experience in both academic and industry and biotech environments.