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PhD Studentships

For additional information on any of these studentships, please contact the supervisor concerned.
To apply, please use the postgraduate Direct Applications Portal.

This is page one of two.  Page two.

There is a possibility that these projects may be DEL funded (Department for Employment and Learning Studentships).  For further information on eligibility for funding, please visit the DEL website.

The closing date for applications unless otherwise stated is: 23 January 2015.

Title:  The epigenetics of evolution: Probing the function of histone H3 K36 methylation in fungal evolution

Background
In this exciting, post-genomic era biologists are obtaining significant insights into the molecular composition of life.  Using comparative genomics we are, for the first time, able to identify sequence differences between species that allow us to make hypothesis as to the molecular basis of their differences.  This provides us with new insights into how evolution works at the molecular level.

We are interested in how the regulation of gene expression, dictated specifically by histone post-translational modifications, has contributed to differences among a class of single celled yeast species from the Saccharaomycotina phylum.  Histones are the building bocks of eukaryotic chromatin and are known substrates for enzymes that acetylate, methylate and phosphorylate.  These histone modifications regulate how chromatin is structured inside the nucleus and have a significant impact on gene expression.  Using bioinformatics, we have found that an enzyme called Jhd1p, which regulates the histone modification, Histone H3 lysine 36 methylation (H3K36me), has been under positive selection in certain yeast species suggesting that it played an important role in the evolution of these species.  The overall goal of this PhD studentship is to understand the evolutionary benefit of Jhd1p and its impact on H3K36me across 11 different yeast species.

Research Aims

  1. To undertake comparative epigenomics and compare genome-wide patterns of histone H3K36me across 11 yeast species using ChIP-seq
  2. To probe the effects of deleting the orthologous genes encoding Jhd1p in 11 yeast species at the level of (a) fitness, (b) gene expression and (c) H3K36me
  3. To resurrect the ancestral version of the gene encoding Jhd1p using phylogentics and synthetic biology, and use it to understand how the function of the Jhd1p enzyme has evolved
The closing date for above project is: 6 February 2015.

Title:  Immune-affinity diffusive sampling of biological fluids for alfatoxin exposure
Supervisors:
 Dr Paul Williams and Dr Yun Yun Gong

Background
Alfatoxins are widely dispersed highly carcinogenic agents, which consistently contaminate food and feed supplies (Gong et al. 2002).  Epidemiologically linked to increased incidences of liver cancers, especially in Asia and Africa (Gong et al. 2004), their complex & costly preparative, storage and analytical procedures hamper rapid and effective monitoring in the places that require them most urgently.  Dietary measurement of alfatoxins alone fail to provide a complete picture of overall exposure burden.  Only by bio-monitoring of biological fluids, such as urine, can an individual or group's exposure incidence truly be assessed (Ezekiel et al. 2014).

Diffusive sampling (DS) relies on the passive/unassisted molecular transport of target analytes through a diffusive surface (sampler) onto an absorbent (storage).  Capture can be tailored for specific alfatoxins and their derivatives by the adoption of selective sampler layers (sample clean-up) combined with monoclonal antibody binders (preconcentration) (Everly et al. 2007).  Altering the combination of sampling layer and binder enables the device to quantify a range of species of interest in human and animal risk assessment.

Being compact, portable and inexpensive DS devices can be applied to a large number of samples (Williams et al. 2011).  Sampling passively provides both a better reflection of in situ trends, but also potentially helps to stabilise and protect against analyte degradation & metabolism, whilst simplifying sample transport.

Research Aims

  1. Develop and test DS samplers for common and problematic alfatoxins and their derivatives
  2. Determine substance specific sampling rates, the effect of pH, ionic strength, boundary layer thickness on substance uptake
  3. Characterise species-specific diffusion coefficients for individual sampler layers, evaluate binder capacities and rates of species transformation
  4. Validate the method for human and animal urine measurement against traditional sampling approaches
  5. Field test the DS samplers as an monitoring tool in the environment

Title:  Technology to tumour-imaging and mapping
Supervisors:
 Dr John Nelson and Dr Bob Pollard, School of Mathmatics and Physics (QUB)

Background
A QUB invention - a gold nanorod chip - has been developed as a biosensor surface that has been incorporated into a single-channel research instrument.  The aim of the project is to build on the expertise in nanomanufacturing and chip design in the development of advanced surface plasmon resonance mapping and imaging of malignancy markers.

Title:  Biomarker development for assessing nature toxins effect on human health
Supervisors:
 Dr Yun Yun Gong and Professor Chris Elliott

Background
Many nature toxins in our food and drink are of carcinogenic potent when chronical exposure at a high level occurs, examples including aflatoxins, heterocyclic amines, microcystins, etc.  A valid biomarker would allow assessment of these toxins intake throughout life time and studies of exposure contribution to cancer development.  A good example of this is that aflatoxin biomarker has improved our understanding greatly on aflatoxin contribution to liver cancer.  The research will involve animal study if necessary to identify, verify, and validate significant biomarkers of nature toxins.  The identified biomarker will be applied to human samples to further confirm its validity for applying in human health studies.  Specifically the project will first establish a library of blood and tissue samples from animal dosed with natural toxins, then conduct metabolomic analysis of these samples to discover new biomarkers of exposure.  The identified biomarkers will be measured using purposely developed ELISA or microarray technique for high throughput detection.  Finally further validation will be conducted in another set of animal or human samples.

Research Aims
We propose to develop biomarkers of natural toxins of great human health concern, using both targeted and untargeted approaches.

Title:  Functional genomics of grasses to study plant adaption to extreme environments using high throughput sequencing approaches
Supervisors:
 Professor Andrew Meharg and Dr Caroline Meharg

Background
The next generation sequencing revolution now provides an unparalleled opportunity to understand the mechanisms of organismal evolution.  Some of the best exemplars of micro-evolutionary change are adaption of certain plant species to hostile soil and environmental habitats where the same species is found in "normal" and "extreme" ecological niches.  De novo Transcriptome assembly is a rapid and relatively cheap way of identifying genes that are different in function and/or differentially expressed between genotypes and we have used to this approach already to study arsenic tolerance in the wild grass Holcus lanatus.  This common grass is adapted to many extreme environments besides arsenic, namely: acid bogs, calcareous grasslands, dune and other maritime locations, Serpentine soils and lead, zinc and copper impacted soils.  By understanding the molecular mechanisms and genetics involved in plant adaptation to salt, acid/alkalinity or toxic metals (some of which are also essential plant and human nutrients), genes lost from crop plants through intensive breeding can be rediscovered, ultimately enabling the breeding of more sustainable crops and extending the agronomic environments capable of supporting crops, given that climate change is impacting soils in a negative way, i.e. towards them to being more extreme with respect to maintaining crop yields.

Research Aims
Grass ecotypes adapted to various abiotic stresses will be de novo transcriptome and genome sequenced and bioinformatics will be employed to identify genes involved in extreme adaption to salt/serpentine/metal impacted habitats.  PCR based approaches will be employed to identify penetrance of those genes in other populations.  Physiological relevance will be followed using rtPCR, proteomics and chemical analysis approaches on contrasting ecotypes exposed to a number of relevant stresses.

Title:  Emerging diseases, biosecurity and zoonoses
Supervisors:
 Dr Nikki Marks and Dr Mike Scantlebury

Background
Recently the number of 'exotic' diseases, such as Blue Tongue, Schmallenberg virus and Equine Infectious Anaemia (EIA) have either been detected for the first time and/or increased in prevalence within the UK (including Northern Ireland).  Added to this is the growing threat of emerging parasite species and anthelmintic resistance which impact both wildlife, domestic, and agricultural livestock, undermining animal health and welfare.  Several factors have been implicated in the introduction and establishment of novel pathogens including: an increase in intensive farming practices, increased animal importation, climatic changes, the relaxation of pet passport controls and a lack of screening of putative wildlife vectors/reservoirs.  Despite the increase in the number of emerging diseases, the Veterinary Laboratories Agency (VLA) reports that surveillance for non-notifiable or emergent diseases is, at best, haphazard.  There are key gaps in our understanding of the animal determinants for emergence and the ability to contain such pathogens, both major obstacles to preventing and/or controlling new disease outbreaks/impacts.  The key diseases and parasite species most likely to pose a significant biosecurity threat have been identified for study within this research project and will be assessed using immunocytochemical, epidemiological, field sampling and molecular techniques which will complement ongoing projects in these areas.

Research Aims
The aim of this PhD studentship is to evaluate both current and emerging pathogenic and zoonotic diseases, identify new biosecurity measures that could be put in place to alleviate/prevent spread and identify areas of potential high risk.  The student will combine field studies and disease screening using well developed platforms to establish the prevalence of disease in wildlife reservoirs, livestock and domestic and agricultural animals which will culminate in the production of disease maps.

Title:  Metabolic enzymes of the liver fluke:  old targets for new drugs
Supervisors:
 Dr David Timson and Dr Kostya Panov

Background
Metabolic enzymes are increasingly considered as potential drug targets for the treatment of infectious diseases.  Indeed, the anthelminthic drug, Clorsulon acts by inhibition of two Fasciola hepatica (liver fluke) glycolytic enzymes - phosphoglycerate kinase (PGK) and phosphoglycerate mutase (PGM).  However, very little is known about the drug's interactions with these two proteins.

The student will create recombinant expression systems for these enzymes and use the bacterially produced proteins to quantify their inhibition by Clorsulon.  Site-directed mutagenesis will be used to identify residues which are important in enzyme-drug recognition.  These studies will be complemented by collaboration with the structural biology group of Prof Jenny Littlechild (Exeter University):  this will enable the student to participate in solving the x-ray crystal structure of the drug-enzyme complex.  In collaboration with a computational chemist (Dr Steffen Lindert, UCSD), the student will identify and test novel inhibitors of the enzymes.  The student will also construct yeast-based "models" in which the yeast's own enzymes are substituted for the fluke enzyme.  This will enable testing of compounds in a cellular environment (since no liver fluke cell culture system is available).

If time permits, the project will be extended to cover other metabolic enzymes according to the student's interests.

Research Aims

  1. Investigate the biochemical and structural basis of Fasciola hepatica phosphoglycerate kinase and phosphoglycerate mutate inhibition by Clorsulon and thus understand how the drug selectively binds parasite over mammalian enzyme.
  2. Discover new compounds which inhibit these enzymes; test selectivity for fluke enzyme over human
  3. Develop a yeast "model" for F. hepatica PGK and PGM and use this to test compounds in a cellular environment
  4. Extend the approaches to other enzymes, as appropriate
Title:  Liver fluke development - A target for parasite control?
Supervisors:
 Professor Aaron Maule and Dr Nikki Marks

Background
Liver fluke are responsible for the disease fasciolosis which undermines animal health across temperate and tropical regions, causing serious losses to the agri-food sector estimated to be in the tens of billions of dollars per year.  In addition to their impact on animal health, liver fluke are zoonotic, infecting an estimated 17 million people such that fasciolosis has been designated as a neglected tropical disease by The World Health Organisation.  Control is fragile, relying largely on the drug triclabendazole, the efficacy of which is being undermined by the rapid development and spread of drug resistance in fluke.  Our laboratory at Queen's was the first to develop gene silencing methods for liver fluke and this project aims to exploit this technology platform in a functional genomics approach to the discovery of new drug targets for next generation flukicides.  Specifically, this project will investigate key genes involved in fluke developmental processes. We have developed methods that allow us to maintain fluke in vitro for periods in excess of 6-months and we can experimentally trigger growth and the cessation of growth.  Here we will identify and characterize the receptors involved in triggering growth as these have significant potential as targets for novel flukicides.  Disrupting fluke growth would prevent the establishment of infection.

Research Aims
The overarching aim is to compromise normal liver fluke growth through the dysregulation of developmental processes in infective stage worms.  There are three specific aims:

  1. Optimize bioassays to interrogate the growth of liver fluke juveniles in vitro
  2. Use RNAi in a functional genomics approach to screen for developmental genes that are critical to fluke growth
  3. Identify the factors that trigger liver fluke growth in vitro.  Use these growth triggers on RNAi-fluke to identify those receptors that switch on developmental processes

Title:  Exploiting microbial enosymbionts of parasites as a target for parasite control
Supervisors:
 Dr John McGrath and Dr Angela Mousley

Background
Diminishing returns are threatening the local pig industry and parasitism has a major impact on productivity in this sector.  Here we propose to investigate the relationships between the most important parasite of pigs, Ascaris suum and bacteria, which are now recognised to be essential to the survival of many parasites.  This work aims to exploit parasite-associated bacteria as a novel target for parasite control.  Previously we have, for the first time, isolated a number of bacteria from both the pseudocoelomic fluid and cuticle of A. suum.  However, this study was limited in its sole use of traditional culture-dependent techniques which are known to considerably underestimate microbial diversity.  We now wish to expand this research by applying state-of-the-art culture independent microbial molecular ecology techniques to ascertain the microbial diversity present within A. suum.  This will ultimately lead to the assessment of the role played by these microorganisms in nematode survival.  The effect of a range of antimicrobial compounds on the survival of A. suum will also be assessed as will the effects those antimicrobial compounds secreted by A. suum have on bacteria.  Ultimately this may lead to the development of alternative therapeutic strategies for the control of A. suum infection.

Research Aims
Within this studentship we will:

  1. Assess the microbial diversity associated with A. suum (0 - 16 months) using both Denaturing Gradient Gel Electrophoresis (DGGE) and through construction of a clone library
  2. Carry out microbial in situ identification (16 - 20 months) using epifluorescent microscopy and fluorescent in situ hybridisation (FISH)
  3. Isolate microorganisms from A. suum (20 - 36 months) and assess their antibiotic sensitivities

Title:  In situ diagnostics for multiple allergens in food
Supervisors:
 Dr Katrina Campbell, Professor Chris Elliott and Dr Mark Mooney

Background
Food allergy is an abnormal response to a foodstuffs triggered by the body's immune system.  Each year, millions of persons globally have allergic reactions to food.  Most allergic reactions cause relatively mild symptoms but some can be life-threatening.  Strict avoidance of food allergens and early recognition and management of allergens in foods are important measures to prevent serious health consequences.  Rapid in situ multiplex diagnostics for the detection of allergens in food products would allow for valuable management of processes in food production and contamination prevention and monitoring.

Several immunoassay methods have been reported for the detection of allergens in foods but are designed to test for single allergens in a sample whereas different types of allergens may be present. Current approaches to allergen testing can be laborious and time-consuming, requiring individual assays for each allergen to be determined. An efficient system would be to utilize a multiplex approach whereby several different allergens can be detected in a single assay. Ideally, such an assay would be simple and rapid, permitting an initial screening of samples in situ in order to identify which allergen(s) are present, to be followed up with a confirmatory test and identification of the allergenic component.

Research Aims
The project aims at the development and assessment of the multiplex detection of key regulated food allergens.  Antibody microarrays using planar waveguide-based fluorescence analysis and additional multiplexing approaches will be investigated.  The scientific and technical objectives are:

  1. Production of antibodies for food allergens
  2. Design of a single rapid sample preparation technique for multiple allergens
  3. Assay development, assessment, and evaluation of food samples
  4. Comparison of methods with the state of the art