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PhD Studentships 2

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 two of two.  Page one.

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 was: 14 January 2013.

Title:  Novel biosignatures for life detection on Mars
Supervisor:  Dr John Hallsworth.

Background
Searches for life on Mars have thus far targeted extinct water courses because water, as far as we know, plays a central role for all life systems.  This project is designed to re-examine our definition of life/ life-signatures here in Earth, and then develop scientific and technological approaches (based on hitherto enigmatic interactions of organic molecules) that can be utilized for future mission(s) to locate and identify life - or its biosignatures - on Mars.  John Hallsworth is an Environmental Microbiologist who has an ongoing collaboration with the Director of NASA’s Astrobiology Program as well as other research groups in the UK, USA, South Korea and India that have complimentary expertise in the fields of geochemistry, polymer science, systems biology and biosensor technology.  The project would suit good candidates with a background in a field such as microbiology, biological sciences, organic chemistry, geochemistry, or biochemistry.

Research Aims
The project aims to identify and define novel biosignatures for life systems based on water: macromolecule interactions.  It will explore and utilize the way in which chao- and kosmotropic activities of environmental solutes impact the hydration and integrity of cellular structures or biomacromolecules, and will involve the development of a chao-/kosmotropicity biosensor.  Ultimately new approaches will be produced that redefine and identify life and its biosignatures based on association with liquid- and molecular water.

Title:  Recovery and recycling of phosphorus from waste
Supervisors:  Dr John McGrath and Dr John Quinn.

Background
This PhD studentship will assist with the development of an innovative approach to two key, related issues of phosphorus (P) sustainability - P supply and P pollution.

P is a scarce natural resource with current estimates suggesting P-rock reserves may only last 80 years.  Paradoxically human exploitation of P has led to an increase in environmental problems associated with its disposal.  The Urban Wastewater Treatment Directive (UWTD) requires P to be removed from sewage to prevent eutrophication: the most widespread threat to good water quality globally.  Implementation of the UWTD, from a water companies’ perspective, results in the production of a P-rich waste.  However for industries which utilise P as a raw material these sludges could potentially be a valuable resource.  Recovery of ‘waste P’ would have significant advantages in terms of sustainable development and the economics of P-processing.  Research at Queen’s focuses on how microorganisms cycle and store P.  We have developed a simple and efficient technology which stimulates environmental microorganisms to store P as a biopolymer known as polyphosphate.  The aim of this PhD studentship is to assess the potential of this system for biological P removal from waste and its recovery as a high value commodity.

Research Aims
Within this studentship we will:

  1. Assess the potential for commercial exploitation of the process as a P removal / recovery system using laboratory (2 litre) bioreactors.
  2. Use axenic cultures to dissect the scientific basis of the phenomenon through study of the composition of the accumulated P, the enzymes involved in its metabolism, and the environmental triggers which stimulate its accumulation/breakdown (as a route to P removal and recovery).

Title:  The genes and enzymes of organophosphorus metabolism in marine bacteria
Supervisors:  Dr John Quinn and Dr John McGrath.

Background
Phosphorus (P) is an essential nutrient, normally found in the environment as inorganic phosphate (Pi); a shortage of Pi in many oceanic surface waters limits marine productivity.  However our recent work has indicated that dissolved organic P (DOP) is also of great importance in the P economy of the oceans.  We believe that the ability of certain groups of microorganisms to degrade organophosphorus compounds using specialized enzymes may play a key role in global P cycling [Quinn et al. (2007) Environ. Microbiol. 9: 2392-2400; Gilbert et al. (2009) Environ. Microbiol. 11:111-125; Villarreal-Chiu et al. (2012) Frontiers in Microbiology, 3: 19].

Marine DOP is composed of organophosphonates, which contain a direct carbon to phosphorus (C-P) bond, and organophosphates which contain a carbon-oxygen-phosphorus (C-O-P) bond. We have already described three novel organophosphonate-degrading enzymes, and bioinformatic analysis indicates the likelihood that a number of other previously-undescribed organophosphate and organophosphonate degradative pathways are present in marine microorganisms.  In this project we want to identify and characterize these.  Besides their role in maintaining the productivity of the oceans, the organisms and enzymes that metabolize C-P and C-O-P compounds may also have important biotechnological applications on-shore, in the detoxification of many recalcitrant organophosphorus pesticides and herbicides.

Research Aims
We aim to exploit those P-scavenging strategies in marine bacteria that allow them to degrade recalcitrant organophosphorus compounds and to store their P-content as intracellular polyphosphate.  We will use in vivo and in silico screening strategies to identify such strains; their polyphosphate kinase, phospho-esterase or C-P lyase activities would be of biotechnological interest eg in the ‘polishing’ of treated effluents or in the mineralization of environmental pollutants such as methyl- and dimethylphosphates and the herbicide glyphosate.

Title:  The role of JMJD2 family of histone demethylases in the regulation of ribosome biogenesis in cancer cells
Supervisors:  Dr Konstantin Panov and Dr David Timson.

Background
The amount of ribosomal RNA (rRNA) produced by RNA Polymerase-I (Pol-I) is rate-limiting to ribosome biogenesis.  Consequently, rRNA levels play a major role in influencing the cellular capacity for protein synthesis placing Pol-I transcription in control of the rate of cell growth and proliferation.  rRNA transcription is tightly regulated in response to changes in cellular metabolism.  Down regulation and re-activation of rRNA synthesis in respond to starvation and re-feeding respectively leads to changes in the methylathyon status of specific histone substrates and perhaps components Pol-I transcription machinery.

In this project, the student will use combination of in vitro and in vivo approaches to analyse the involvement of histone demethylases (members of JMJD2 family) in metabolically driven activation of rRNA synthesis by different stimuli (i.e. growth factors, insulin, hormones).  In parallel, the student will investigate known substrates of JMJD2 family aiming to determine if any of these are modified as consequence of activation.  Further studies will be carried out aiming to determine if components of Pol-I transcription apparatus are substrates to JMJD2 demethylases. The project will permit considerable flexibility for the student, with the opportunity to develop further research interests relating to methabolic dependent regulation of transcription in cells.

Research Aims

  1. Using siRNA investigate which members of JMJD2 family involved in activation of rRNA synthesis/processing by specific stimuli in different cancer cells.
  2. Perform similar study to determine if these enzymes involved in metabolic driven repression of rRNA synthesis/processing.
  3. Using ChIP with specific histone antibodies determine if known substrates of particular demethylase are modified during activation/repression.
  4. Expand this analysis of components of Pol-I transcription machinery using MS approach.

Title:  Using Metagenomic Approaches to Predict Evolution of Microbial Communities
Supervisors:  Dr Leonid Kulakov and Dr Chris Allen

Background
Understanding the development and evolution of bacterial communities has a primary significance for many biological disciplines and industries including medicine, agriculture and waste treatment.  As the majority of microorganisms inhabiting natural environments are not readily cultivable in the laboratory, metagenomic approaches have became the cornerstone of modern environmental and industrial microbiology.

Bacteriophages (bacterial viruses) constitute a major part of all known microbial communities; they effectively control the size and composition of bacterial populations.  Our recent studies (e.g. Applied Environmental Microbiology 2011, v 77 p 5529) clearly demonstrates that comparative analysis of phage and total bacterial metagenomes derived from the same environment could constitute an efficient approach for the studying genetic processes occurring in microbial communities.  Analysis of the metagenomic data collected over an extended period of time has allowed us to conclude that dynamic changes in phage populations could be used to forecast development of the bacterial community including prediction of the future dominant species.  This represents a fundamental step forward in our ability to predict microbial community development: this has fundamental implications in, for example, predicting the effects of climate change on microbial communities or evaluating the efficiency and robustness of industrial biotechnological processes.

Research Aims
The main aim of the proposed research will be the development of a metagenomic based tool to forecast the future development of complex microbial communities and predict the evolution pathways for key bacterial species. To achieve this the following tasks will be undertaken: i) total bacterial and bacteriophage metagenomes will be isolated from the selected environment over 1 – 2 year period; ii) key genetic markers will be identified and tested; iii) the approach will be tested using continuous culture experiments.

Title:  Investigating how dietary endocrine disruptors are involved in the pathogenesis of diabetes and obesity
Supervisors:  Dr Lisa Connolly and Dr Brian Green

Background
Endocrine disruptors (EDCs) interfere with the normal functioning of the endocrine system.  This can lead to detrimental health effects such as cancer and infertility.  One of the most important exposure routes to EDCs in via the diet.  Recently, EDCs have been linked to the rising western levels of diabetes and obesity and it is established that EDCs are involved in adipogenesis and energy metabolism.  EDCs are diverse both in their chemical structure and their mechanism of action.  Commonly proposed mechanisms involve direct binding to nuclear receptors and disruption of hormone signaling via enzymes and genes.

The gut is a major source of endocrine hormones and in fact is the largest endocrine organ in the body, and the effect of EDCs within the gut is extremely understudied.  Although investigations into the role of EDCs in obesity have focused mainly on interactions of EDCs with the fetus during susceptible windows of programmed development, several other targets/ mechanisms are involved.

This project proposes that common dietary EDCs (e.g. bisphenol A, dioxins etc.) interact with enteroendocrine cells lining the intestine and their disruption of gut hormone secretion and/or signaling could impair glucose homeostasis and satiety responses.

Research Aims

To assess whether common dietary endocrine disruptors can affect:

  1. The synthesis and secretion of gut hormones that regulate glucose homeostasis or satiety responses.
  2. Lipid homeostasis (adipogenesis, lipolysis and lipogenesis).
  3. Body weight, glucose tolerance and insulin sensitivity in vivo.

Title:  Biochemical characterisation and molecular function of Trichinella spiralis cathepsin F
Supervisors:  Dr Mark Robinson and Professor Aaron Maule.

Background
Cysteine peptidases, such as cathepsins B, F and L, are ubiquitously expressed by parasitic worms and have key roles in parasite virulence including tissue migration, feeding and suppression of host immune responses.  They are the most abundant molecules found in parasite secretions and, as such, are important targets for anti-parasite drugs.  We have identified a novel cathepsin F (TsCF) that is secreted by the nematode parasite, Trichinella spiralis.  The digestive activity of most cathepsin peptidases is regulated by an N-terminal extension, or prosegment, that blocks the active site.  However, TsCF possesses an additional N-terminal domain with similar sequence to the cysteine peptidase inhibitor, cystatin.  This domain arrangement is unusual having been reported in only a few other species.  We have found that expression of TsCF is restricted to the Trichinella newborn larvae that migrate via the bloodstream and infect, and encapsulate within, host skeletal muscle cells.  This raises the intriguing possibility that TsCF uses its cystatin domain to suppress host immune responses during migration in the blood and its peptidase activity to facilitate invasion of host skeletal muscle cells.  In this project we will produce functionally active recombinant TsCF and investigate its role in Trichinella biology.

Research Aims
The project has three major aims:

  1. Biochemical characterisation of TsCF including its mechanism of activation/prosegment removal and substrate specificity.
  2. Investigate the role of TsCF in the host-parasite interaction through immuno-localisation, peptidase-substrate assays and inhibitor studies.
  3. Investigate the function of the TsCF cystatin domain in terms of its ability to inhibit mature TsCF and/or host cysteine peptidases such as those involved in antigen processing.

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 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 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:  Emerging Diseases, Biosecurity and Zoonoses
Supervisors:  Dr Tassos Koidis and Professor Chris Elliott.

Background
Every year more than 30m litres of olive oil are consumed in UK households partly due to the health claims associated with the ‘Mediterranean diet’ and partly due to olive oil’s unique flavour.  On the other hand, wine consumption is even higher (>150m litres) with the majority imported from overseas.  With such high volumes, confirmation of originality and detection of fraud are becoming hugely important.  In the case of olive oil, it can be adulterated with hazelnut oil or lower cost /quality oils but still meet most of the classification criteria.  In the case of wine, confirmation of geographic location often linked to PDOs and PGIs is also important for consumer’s awareness of the origin.  Apart from that, several emerging risks can be associated with these products such as potential contamination (wines) or a non-fully-explained allergenicity in some refined olive oils adulterated with nut oils.  In UK Customs, however, analyses of sophisticated fraud and other modern authenticity indexes rely on established standard high cost and laborious chromatographic methods and inevitably in paperwork.  There is a need to develop novel analytical fingerprint based methods that are able to assess olive oil and wine authenticity and integrity in place using low cost equipment such as spectroscopic systems.

Research aims including economic relevance

  • To develop novel and fingerprint methods to detect geographic origin, adulteration and presence of contaminants and potential allergens in imported olive oil and wine.
  • Apply chemometrics to this wide range database to create robust models that classify unknown imported samples in the UK.
  • Validate the methods through replication of scenarios of olive oil and wine mishandling.
  • To equip UK Customs and Public Analysis with low cost analytical methods that would ultimately provide consumer confidence for the wine and olive oils consumed in the UK.

Fraud detection methods developed will benefit regulatory authorities such as DEFRA and the Public analysts.