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

Cell behaviour

Supervisor: Dr Marcus Bischoff

Research area(s): Cell behaviour

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 the mechanisms underlying the coordination of cell behaviours using the adult abdominal epidermis of Drosophila as a model. Employing a combination of in vivo 4D microscopy, cell biology techniques and sophisticated genetics, we study cytoskeletal dynamics that underlies behavioural plasticity. These insights will be of widespread relevance, since the (mis-) regulation of cell behaviour is also fundamental to wound repair and numerous diseases, including cancer.

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

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

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

Towards an understanding of ISG15 and innate immunity

Supervisor: Dr David Hughes

Research area(s): Towards an understanding of ISG15 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 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

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:

Subject area(s): Virology, Innate Immunity

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

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

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: 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

 

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.