MSc(Res) Biomedical Sciences

The Master of Science by Research degree in Biomedical Sciences is a 12-month, research only degree, in which the candidate will undertake a supervised research project in the broad area of Biomedical Sciences, in the School of Biology, University of St Andrews.

The candidate will be based in the interdisciplinary Biomedical Sciences Research Complex (BSRC), based at the North Haugh Science Campus, St Andrews. The BSRC comprises research groups undertaking highly innovative, multi-disciplinary research in eleven broad areas of biomedical research, employing state-of-the-art techniques to address key questions at the leading edge of the biomedical and biological sciences.

Eleven research themes run through the BSRC: Biophysics; Chemical Biology; Chemistry; Enzymology; Microbiology; Molecular Biology; Molecular Medicine; Parasitology; Structural Biology; Translational Biology; Virology. These interdisciplinary approaches bring together molecular biologists, chemists, computer scientists, geneticists, bioinformaticians and clinicians to challenge and further our understanding of disease, in terms of basic biological function through to medical intervention. Further details about the BSRC.

Candidates may approach potential supervisors in the BSRC directly or via advertised projects listed below.

Projects

Investigating the coordination of cell behaviours during Drosophila morphogenesis

Supervisor: Dr Marcus Bischoff

Research area(s): Investigating the coordination of cell behaviours during Drosophila morphogenesis

Research description: 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.

Subject area(s): Cell Biology, Genetics

Keywords: cytoskeletal dynamics, cell migration, Drosophila, in vivo microscopy

Manipulating bacterial populations with cyclic peptides

Supervisor: Dr Clarissa Czekster

Research area(s): Manipulating bacterial populations with cyclic peptides

Research description: 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. We work with pathogenic bacteria that contribute to the problem of antimicrobial resistance such as Staphylococcus aureus and Pseudomonas aeruginosa. Our 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).

Relevant references:

Subject area(s): Biochemistry, enzymology

Keywords: protein biochemistry, antimicrobial peptides, biocatalysis, biofilms

Identifying novel treatments for antibiotic resistant bacteria

Supervisor: Dr Peter Coote

Research area(s): Antibiotic resistant bacteria; Identifying novel treatments for antibiotic resistant bacteria

Research description: Utilise an invertebrate model (Galleria mellonella – wax-moth larvae) to study bacterial/fungal infections in vivo :

  1. Determine the efficacy of drug treatments versus human pathogens in vivo, eg. Mycobacterium , Multi-drug resistant (MDR) Gram –ves such as Pseudomonas aeruginosa.
  1. Identify novel, synergistic, combination treatments in vivo.
  2. Study the selection of antibiotic resistance in vivo and characterise the effect of antibiotic resistance on microbial ‘fitness’ and virulence during infection.
  3. 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: Desbois, A.P. and Coote, P.J. (2012) Utility of greater wax moth larva (Galleria mellonella) for evaluating the toxicity and efficacy of new antimicrobial agents. Advs. Appl. Microbiol. 78: 25-54. DOI: 10.1016/B978-0-12-394805-2.00002-6.

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.

Dougal H. Adamson, Vasare Krikstopaityte & 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.

Subject area(s): Antibiotic resistance

Keywords: MDR Gram –ve bacteria; invertebrate infection model; Galleria mellonella; Pseudomonas aeruginosa; Klebsiella pneumoniae; Escherichia coli; antibiotics; combination therapy

Remodelling chromatin during cellular senescence and survivor formation

Supervisor: Dr Helder Ferreira

Research area(s): Remodelling chromatin during cellular senescence and survivor formation

Research description: Telomeres are protein-DNA structures that protect the ends of linear chromosomes. Telomeres shorten every time cells replicate. When they reach a critically short length, telomeres activate signals resulting in cellular senescence or death. Stem cells and cancers need to overcome this inbuilt limit to become immortal. Recent evidence has implicated chromatin regulators as factors that affect how cells can become immortal. Yet, we know relatively little about the underlying changes in chromatin structure as this happens. This project, in budding yeast, will involve training in genetic modification as well as chromatin isolation and analysis of next generation sequencing data data.

Relevant references:

Subject area(s): Molecular biology

Keywords: Telomere, chromatin, genome stability, aging

Investigating the role of sumoylation during telomere elongation

Supervisor: Dr Helder Ferreira

Research area(s): Investigating the role of sumoylation during telomere elongation

Research description: 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.

Relevant references:

Subject area(s): Molecular biology

Keywords: Telomeres, SUMO, genome stability, DNA repair

Evolutionary developmental biology

Supervisor: Dr David E. K. Ferrier

Research area(s): Evolutionary developmental biology

Research description: We seek 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. A variety of invertebrate species are studied (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: See https://synergy.st-andrews.ac.uk/edge/

Subject area(s): Evolutionary biology, Developmental Biology

Keywords: Evo-devo, regeneration, embryology, genomics

Mechanisms of bacterial enzymes: towards novel antibiotics

Supervisor: Dr Rafael Guimaraes da Silva

Research area(s): Mechanisms of bacterial enzymes: towards novel antibiotics

Research description: 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, site-directed mutagenesis.

Relevant references:

Subject area(s): Biochemistry, Enzymology

Keywords: mechanism, kinetics, antibiotics, crystallography

Dissecting the chemistry of cold- and warm-adapted enzymes

Supervisor: Dr Rafael Guimaraes da Silva

Research area(s): Dissecting the chemistry of cold- and warm-adapted enzymes

Research description: Enzymatic reaction rates increase exponentially with temperature. Nonetheless, cold-adapted enzymes have 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 and purification of isotope-labelled molecules.

Relevant references:

Subject area(s): Biochemistry, Enzymology

Keywords: mechanism, kinetics, crystallography, catalysis

Structure, mechanism and function of carbohydrate processing enzymes

Supervisor: Dr Tracey Gloster

Research area(s): Structure, mechanism and function of carbohydrate processing enzymes

Research description: 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).

Relevant references:

Subject area(s): biochemistry, structural biology

Keywords: carbohydrates, enzymes, structure, mechanism

Does dementia occur in sea mammals?

Supervisor: Professor Frank Gunn-Moore

Research area(s): Does dementia occur in sea mammals?

Research description:

A new Masters position is available to explore the question does dementia occur in sea mammals? Alzheimer’s disease in humans is a well-known phenomenon, but whether this form of dementia occurs in other mammals has only been explored in relatively small numbers, and very few other mammals have been potentially shown to have biochemical markers that look similar to those found in human patients (Youssef et al., 2016 Veterinary Pathology 53(2) 327-348). Recent data involving work from Florida, St Andrews and Oxford has suggested that these biomarkers may also be found in some species of stranded dolphins (Gunn-Moore et al., 2018 Alzheimer’s & Dementia, 14(2), 195-204). Therefore in this exciting and novel proposal due to a new collaboration between Prof Frank Gunn-Moore (Biomedical Science Research Complex, University of St Andrews), Prof Ailsa Hall (Director of the Sea Mammal Research Unit, University of St Andrews), Sir Prof Simon Lovestone (University of Oxford) and Dr Mark Dagleish (Moredun Research Institute, Edinburgh), we seek a candidate to explore a unique data base of sea mammal brains for the presence of potential biochemical changes that are associated with Alzheimer’s disease and other dementia. For enquiries, please contact: fjg1@st-andrews.ac.uk

Closing Date 1st May 2018.

Relevant References:

Subject area(s): Dementia, sea mammals

Keywords: dementia, Alzheimer’s, sea mammals

Molecular Virology and Innate Immunity

Supervisor: Dr David Hughes

Research area(s): Molecular Virology and Innate Immunity

Research description: 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 being offered that are aimed at making a significant contribution to our understanding of the ISG15 system and its interplay with innate immunity.

Relevant references:

Subject area(s): Virology, innate immunity

Keywords: Virology, innate immunity, ubiquitin-like modifications, ISG15

Eukaryotic chromosome replication and genome stability

Supervisor: Dr Stuart MacNeill

Research area(s): Eukaryotic chromosome replication and genome stability

Research description: 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 fission yeast as a model system. Your MSc(Res) project will allow you to gain vital experience in a wide variety of techniques encompassing cell biology, genetics, molecular biology and biochemistry, providing an excellent preparation for future PhD studies in genome stability.

Relevant references: See http://www.st-andrews.ac.uk/~sam31/

Subject area(s): Molecular biology, biochemistry

Keywords: DNA replication, genome stability, yeast, molecular biology

Genome stability: exploring protein sequence/structure diversity on the outermost branches of the Tree of Life

Supervisor: Dr Stuart MacNeill

Research area(s): Genome stability: exploring protein sequence/structure diversity on the outermost branches of the Tree of Life

Research description: Maintaining genome structure and information content across generations is vital for all forms of life, yet detailed understanding of the biology of these processes is confined to a relatively small number of well-studied organisms and does not begin to capture the rich diversity of protein sequence/structure now apparent on the outermost branches of the Tree of Life. This MSc(Res) project will explore this unstudied diversity by identifying and characterising genome stability factors from highly diverged eukaryotic species and viruses, allowing you to gain invaluable experience in molecular biology, biochemistry and bioinformatics and providing an excellent preparation for future PhD studies.

Relevant references: See http://www.st-andrews.ac.uk/~sam31/

Subject area(s): Molecular biology, biochemistry

Keywords: Evolution, bioinformatics, genome stability, molecular biology

Exploring the enzymes and mechanisms of chromosomal DNA replication in the archaea

Supervisor: Dr Stuart MacNeill

Research area(s): Exploring the enzymes and mechanisms of chromosomal DNA replication in the archaea

Research description:

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 archaeon Haloferax volcanii as a model for dissecting archaeal replication. For your Masters you will learn to genetically manipulate Haloferax to explore how gene family expansions have shaped the replication capacity of this model organism. To complement these studies, you will also undertake biochemical analysis of one or more replication proteins.

Relevant references:

MacNeill, S.A. (2018) The archaeal RecJ-like proteins: nucleases and ex-nucleases with diverse roles in DNA replication and repair. Emerging Topics in Life Sciences, doi: 10.1042/ETLS20180017.

Giroux, X. and MacNeill, S.A. (2015) A novel archaeal DNA repair factor that acts with the UvrABC system to repair mitomycin C-induced DNA damage in a PCNA-dependent manner. Mol. Micro., 99, 1-14.

Giroux, X. and MacNeill, S.A. (2015) Inhibiting NAD+-dependent DNA ligase activity with 2-(cyclopentyloxy)-5′-deoxyadenosine (CPOdA) offers a new tool for DNA replication and repair studies in the model archaeon Haloferax volcaniiFEMS Micro. Letts., doi: 10.1093/femsle/fnv181.

Kristensen, T.P., Maria Cherian, R., Gray, F.C. and MacNeill, S.A. (2014) The haloarchaeal MCM proteins: bioinformatic analysis and targeted mutagenesis of the β7-β8 and β9-β10 hairpin loops and conserved zinc binding domain cysteines. Front. Microbiol., 5, 123. doi: 10.3389/fmicb.2014.00123.

Subject area(s): Molecular biology, molecular genetics

Keywords: Archaea, DNA replication, evolution

Molecular herpesvirus biology

Supervisor: Dr Michael Nevels

Research area(s): Molecular herpesvirus biology

Research description: 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. We study how chromatin-based epigenetic processes in the viral and human genome control CMV replication and persistence. We 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.

Subject area(s): VMolecular Virology, Molecular Biology

Keywords: human cytomegalovirus, virus-host interaction, innate immunity, epigenetic regulation

Exploring riboswitches as biosensors and antibiotic targets

Supervisor: Dr Carlos Penedo

Research area(s): Exploring riboswitches as biosensors and antibiotic targets

Research description: Antibiotic resistance is becoming a global threat to human life that causes an increasing number of deaths per year. In this project, we will investigate bacterial gene regulation pathways that involve exclusively mRNA sequences. These mRNA structures, so-called riboswitches, regulate the expression of crucial genes in respond 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 [1,2]. In this project, we will explore some recently discovered riboswitches and their potential in synthetic biology and as antibiotic targets.

Relevant References: [1] Mehdizadeh Aghdam E, Hejazi MS, Barzegar A. Riboswitches: from living biosensors to novel targets of antibiotics, Gene 2016, 592, 244-59

[2] 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.

Subject area(s): Biomedical sciences

Keywords: RNA function, riboswitches, gene regulation, single-molecule microscopy, biophysics

Biotechnological applications of single-strand DNA binding proteins

Supervisor: Dr Carlos Penedo

Research area(s): Biotechnological applications of single-strand DNA binding proteins

Research description: 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 characterized by the presence of an OB-fold (oligonucleotide/oligopeptide/oligosaccharide) binding motif to recognize single-strand DNA. Recently, we have characterized an archaeal single-stranded DNA binding protein and demonstrated its monomeric character, its cooperative mode of action [1, 2] and, strikingly, its ability to efficiently bind RNA [1]. In this project, we will explore potential applications of this protein using synthetic biology and biophysical approaches including cutting edge single-molecule microscopy.

Relevant References: [1] 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.

[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.

Subject area(s): Biomedical sciences

Keywords: Nucleic acids, OB-folds, biophysics, DNA protection, synthetic biology

Single-molecule structural dynamics of protein channels

Supervisor: Dr Carlos Penedo

Research area(s): Single-molecule structural dynamics of protein channels

Research description: 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 organize themselves into a pore structure, partially or fully embedded within the cell membrane [1). In this project, we will use state-of-the art single-molecule fluorescence microscopy and bioconjugation techniques [2] 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: [1] 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.

[2] Wang et al. Structural dynamics of potassium-channel gating revealed by single-molecule FRET. (2016) Nat. Struct. Mol. Bio. 23, 31-36.

Subject area(s): Biomedical sciences

Keywords: Membrane channel proteins, single-molecule, gating mechanism, electron paramagnetic resonance

Enabling high-speed, super-resolution imaging of nucleic acid sequences

Supervisor: Dr Carlos Penedo

Research area(s): Enabling high-speed, super-resolution imaging of nucleic acid sequences

Research description: Enabling high-speed, super-resolution imaging of nucleic acid sequences: Super-resolution imaging techniques are revolutionizing our understanding of biological processes [1]. However, their widespread application to resolve duplex nucleic acid structures (dsNA) from single-stranded regions (ssNA) remains a challenge. In this project we aim to break this limitation by developing an imaging method for NA sequences based on the use of single-stranded binding (SSB) proteins [2,3] as staining agents to obtain high-resolution structural details of nucleic acid sequences as never seen before.

Relevant References:

[1] 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)

[2] 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)

[3] Morten et al. High-affinity RNA binding by a hyperthermophilic single-stranded DNA-binding protein. Extremophiles, 21:369-379 (2017)

Subject area(s): Biophysics, molecular and cellular imaging

Keywords: single-molecule, super-resolution imaging, nucleic acids, single-strand binding proteins

Innate pathogen recognition

Supervisor: Dr Michael M Nevels

Research area(s): Innate pathogen recognition

Research description: 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. We have previously shown that the DNA genome of cytomegalovirus (CMV) is chromatinized differently compared to cellular chromatin. We 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 signaling 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.

Subject area(s): Innate Immunity, Molecular Virology

Keywords: innate immune signalling, DNA sensing, chromatin structure, human cytomegalovirus

Evolutionary biology, developmental biology, cell biology, evo-devo, regeneration biology, genomics

Supervisor: Dr Ildiko Somorjai

Research area(s): Evolutionary biology, developmental biology, cell biology, evo-devo, regeneration biology, genomics

Research description: 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. We predominantly use the marine invertebrate chordate “amphioxus” due to its genetic and anatomical similarly to simple vertebrates. We 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, and phylogenetic analyses. https://synergy.st-andrews.ac.uk/cord/

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 & 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.

Subject area(s): Evolutionary Biology, Developmental Biology

Keywords: Regeneration, Development, Evo-devo, Amphioxus

Towards the use of afamin for delivery of pharmaceuticals across the blood brain barrier

Supervisor: Dr Alan Stewart, School of Medicine

Research area(s): Towards the use of afamin for delivery of pharmaceuticals across the blood brain barrier

Research description: 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 identification of new targets (despite this being where the vast majority of research efforts are focussed) 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, >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 Dbinding protein and afamin) are 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 (e.g.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 it is envisioned that the student would spend some time in their Nottingham-based laboratories, thus gaining research experience in both academic and industry/biotech environments.

Relevant References:

Subject area(s): Cell Biology, Neurology

Keywords: Neurology, pharmaceutics, therapeutics, proteins, protein expression,

Cell biology, neurodegeneration

Supervisor: Dr Judith Sleeman

Research area(s): Cell biology, neurodegeneration

Research description: The main theme of research in our group is the cellular organisation of RNA biology. Our 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). Our key expertise in the group lies in mammalian cell culture and microscopy, including live cell microscopy. Together with our key collaborators in the UK, Canada and Australia, we combine 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.

Subject area(s): Cell Biology, Neurodegeneration

Keywords: RNA biology, Cell nucleus, SMA, DM1

Parasite biochemistry

Supervisor: Professor Terry K Smith

Research area(s): Parasite biochemistry

Research description: 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 novel drug targets, in conjunction with high-throughput screening to identify novel lead compounds.

Relevant References:

Subject area(s): Molecular and Biochemical Parasitology

Keywords: Parasitology, Metabolism, Biochemistry, Lipids

Characterisation of plant membrane contact sites

Supervisor: Dr Jens Tilsner

Research area(s): Characterisation of plant membrane contact sites

Research description: Membrane contact sites are cellular communication hubs at the interfaces of different organelles, where two membranes are held in very close (<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

Subject area(s): Plant cell biology, biochemistry

Keywords: live cell imaging, electron microscopy, protein biophysics, food security

Post-translational modification of plant virus cell-to-cell transport proteins

Supervisor: Dr Jens Tilsner

Research area(s): Post-translational modification of plant virus cell-to-cell transport proteins

Research description: 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. We have 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.

Subject area(s): Molecular virology, biochemistry

Keywords: post translational modification, mass spectrometry, live cell imaging, food security

The molecular biology of the CRISPR-Cas system for antiviral defence

Supervisor: Prof Malcolm White

Research area(s): The molecular biology of the CRISPR-Cas system for antiviral defence

Research description:

Our lab is focussed on the molecular biology of the molecular machines that manipulate RNA and DNA. We utilise a combination of structural, molecular and micro-biology, biochemistry and bioinformatics. We have particular interests in two main areas:

  1. the CRISPR-Cas system of antiviral defence – a fascinating aspect of prokaryotic molecular biology with many fundamental research questions and exciting applications in genome engineering and biotechnology.
  2.  DNA Repair pathways and proteins in humans and archaea. In particular, Nucleotide Excision Repair.

Further information is available at our homepage: https://synergy.st-andrews.ac.uk/crispr/

Relevant References:

Prespacer processing and specific integration in a Type I-A CRISPR system Rollie C, Graham S, Rouillon C and White MF (2018) Nucleic Acids Research 46, 1007-1020. (“Breakthrough Article” top 3%)

 Mechanism of DNA loading by the DNA Repair helicase XPD Constantinescu Aruxandei D, Petrovic-Stojanovska B, Penedo JC, White MF* and Naismith JH* (2016) Nucleic Acids Res 44, 2806-2815.

 Cas6 specificity and CRISPR RNA loading in a complex CRISPR-Cas system Sokolowski RD, Graham S and White MF (2014) Nucleic Acids Res. 42, 6532-41.

 The XPB-Bax1 helicase-nuclease complex unwinds and cleaves DNA substrates: implications for eukaryal and archaeal Nucleotide Excision Repair Rouillon C and White MF (2010) J. Biol. Chem.285, 11013-11022.

Subject area(s): Biochemistry, Molecular Biology

Keywords: DNA Repair, CRISPR, Archaea, molecular machines

The human DNA repair systems: mechanisms of cancer avoidance

Supervisor: Prof Malcolm White

Research area(s): The human DNA repair systems: mechanisms of cancer avoidance

Research description:

Our lab is focussed on the molecular biology of the molecular machines that manipulate RNA and DNA. We utilise a combination of structural, molecular and micro-biology, biochemistry and bioinformatics. We have particular interests in two main areas:

  1. the CRISPR-Cas system of antiviral defence – a fascinating aspect of prokaryotic molecular biology with many fundamental research questions and exciting applications in genome engineering and biotechnology.
  2.  DNA Repair pathways and proteins in humans and archaea. In particular, Nucleotide Excision Repair.

Further information is available at our homepage: https://synergy.st-andrews.ac.uk/crispr/

Relevant References:

Prespacer processing and specific integration in a Type I-A CRISPR system Rollie C, Graham S, Rouillon C and White MF (2018) Nucleic Acids Research 46, 1007-1020. (“Breakthrough Article” top 3%)

 Mechanism of DNA loading by the DNA Repair helicase XPD Constantinescu Aruxandei D, Petrovic-Stojanovska B, Penedo JC, White MF* and Naismith JH* (2016) Nucleic Acids Res 44, 2806-2815.

 Cas6 specificity and CRISPR RNA loading in a complex CRISPR-Cas system Sokolowski RD, Graham S and White MF (2014) Nucleic Acids Res. 42, 6532-41.

 The XPB-Bax1 helicase-nuclease complex unwinds and cleaves DNA substrates: implications for eukaryal and archaeal Nucleotide Excision Repair Rouillon C and White MF (2010) J. Biol. Chem.285, 11013-11022.

Subject area(s): Biochemistry, Molecular Biology

Keywords: DNA Repair, CRISPR, Archaea, molecular machines

Living at extremes: how the archaea repair their DNA

Supervisor: Prof Malcolm White

Research area(s): Living at extremes: how the archaea repair their DNA

Research description:

Our lab is focussed on the molecular biology of the molecular machines that manipulate RNA and DNA. We utilise a combination of structural, molecular and micro-biology, biochemistry and bioinformatics. We have particular interests in two main areas:

  1. the CRISPR-Cas system of antiviral defence – a fascinating aspect of prokaryotic molecular biology with many fundamental research questions and exciting applications in genome engineering and biotechnology.
  2.  DNA Repair pathways and proteins in humans and archaea. In particular, Nucleotide Excision Repair.

Further information is available at our homepage: https://synergy.st-andrews.ac.uk/crispr/

Relevant References:

Prespacer processing and specific integration in a Type I-A CRISPR system Rollie C, Graham S, Rouillon C and White MF (2018) Nucleic Acids Research 46, 1007-1020. (“Breakthrough Article” top 3%)

 Mechanism of DNA loading by the DNA Repair helicase XPD Constantinescu Aruxandei D, Petrovic-Stojanovska B, Penedo JC, White MF* and Naismith JH* (2016) Nucleic Acids Res 44, 2806-2815.

 Cas6 specificity and CRISPR RNA loading in a complex CRISPR-Cas system Sokolowski RD, Graham S and White MF (2014) Nucleic Acids Res. 42, 6532-41.

 The XPB-Bax1 helicase-nuclease complex unwinds and cleaves DNA substrates: implications for eukaryal and archaeal Nucleotide Excision Repair Rouillon C and White MF (2010) J. Biol. Chem.285, 11013-11022.

Subject area(s): Biochemistry, Molecular Biology

Keywords: DNA Repair, CRISPR, Archaea, molecular machines

Entry requirements and selection process

An undergraduate Honours degree at 2:1 level or better in a relevant discipline (e.g. biochemistry, molecular biology, biomedicine, biomolecular sciences, microbiology, virology, 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, and subject to interview by the project supervisor and an additional member of the Biology Postgraduate Committee.

Fees

For details of postgraduate tuition fees relevant to our research degrees including the MSc(Res), please visit:

http://www.st-andrews.ac.uk/study/pg/fees-and-funding/research-fees/

Progression and assessment

Students in the MSc(Res) will be assigned an Internal Examiner (IE) and PG Tutor by the School. There will be a progress review meeting at three months to monitor and evaluate student progression, convened by the IE, with the student and Tutor in attendance. This meeting will be guided by a brief supervisor report and will be based on oral examination with no requirement for a written submission by the student.

The degree requires submission and examination of a dissertation at the end of the one-year program. As per 2016-2017 Senate Regulations (page 9), this thesis will consist of up to 30,000 words. The thesis will be evaluated by the IE and an External Examiner appointed at time of submission. Evaluation will be based on the written submission; there is no requirement for a viva.

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 award-winning University of St Andrews GradSkills program, run by our Professional Development Unit CAPOD.

Specific post-graduate programs run within the School of Biology may also offer additional training, for instance in statistical, bioinformatics or molecular techniques.

Application

Students may apply for placement in advertised projects or contact potential supervisors directly. We strongly recommend that potential candidates make contact with a potential supervisor before applying.  See links on this page.

Biology has two dates for admission to this degree: September and January each year.

If you have decided that 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.

Note: 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: supervisors’ email addresses may be found using the links on this page.