Deadline: Friday 29th June 2012
Stipend: £13,590

There will be up to ten fully funded scholarships available in 2012 to allow suitably qualified candidates to integrate systems biology approaches with whole animal physiology, pharmacology or veterinary science within our popular MRes Biomedical Sciences program. These are funded by The Biotechnology and Biological Sciences Research Council (BBSRC) and the Medical Research Council (MRC). The BBSRC and MRC support systems biology approaches to science as well as promoting training in animal sciences. Glasgow University is one of four centres of excellence in the training of integrative mammalian biology funded by the BBSRC, British Pharmacological Society, KTN, Medical Research Council and Scottish Higher Education Funding Council. Glasgow University also offers a wide range of expertise in Systems Biology. For more details see:

http://www.gla.ac.uk/faculties/fbls/systemsbiology/

As part of the BBSRC and MRC support for these activities, 10 scholarships are available for our one year MRes in Integrative Mammalian Biology/Systems Biology. The scholarships pay an enhanced stipend for living expenses and cover all tuition fees The MRes will follow our highly successful model of two taught modules (taking up about a third of the course) and two projects. One project will involve a systems approach (e.g. mathematical modeling, computing, ‘omics’, bio-engineering) which will be related to or integrated with the physiology/veterinary project in an iterative fashion. The course will be a specialisation within the existing MRes in Biomedical Sciences:

http://www.gla.ac.uk/postgraduate/taught/biomedicalsciences/

Candidates for these scholarships must have at least an upper second class Honours degree or equivalent in a relevant subject (for instance physiology, pharmacology, neuroscience or veterinary medicine but we also welcome students with backgrounds in systems approaches such as mathematical modeling, computing, ‘omics’, bio-engineering) and be eligible by residence for a UK research council studentship (applicants must ordinarily have been resident in the UK for at least three years before applying). Please note that numbers are limited and so this MRes speciality is not available to fee paying students.

All candidates intending to specialise in Integrative Mammalian Biology must already have, or be in a position to obtain before the start of the course, a Home Office licence.

The Studentship will be supervised by staff drawn from the College of Medical, Veterinary and Life Sciences and The College of Science and Engineering.

The following are some examples of previous projects and are indicative of the types of project likely to be available in 2012-2013:

Dr Christopher Loughrey and Prof Godfrey Smith and Prof Xiaoyu Luo

The project will quantify the relationship between the timing of electrical activation of heart with the mechanical response. This will be studied and a corresponding computational model will be created for normal hearts under normal conditions and also in hearts paced from external electrodes placed on the endocardial and epicardial sites and hearts derived from a rabbit heart failure model. This will create sub-optimal timings of electrical and mechanical activation which will be measured and incorporated into the mathematical model. There is a lack of computational models that incorporate electrical and mechanical systems and no studies to date have matched computational and corresponding biological data. Hence a project in this area is likely to quickly yield novel and important data. The first project will be in the in vivo laboratories and involve in vivo and ex vivo haemodynamic and cardiac measurements (MRI, cardiac output measurements, assessment of blood pressures) in the whole animal. The second will use data derived from these experiments and will be held with Prof Luo in Mathematics (mathematical modelling).

Prof Jon Cooper and Prof Mandy MacLean

By using microfabricated sensors with patterned macromolecules biosensing elements we can understanding and predict complex interactions between cells, their immediate environment and signalling molecules. We propose the development of such technology and demonstrate its application in vivo. One example is the complex response of pulmonary arteries to a hypoxic insult. This results in pulmonary vascular remodelling. It is not currently possible to examine these complex interacting phenomena in vivo, in real time. We will demonstrate the utility of multi-sensor biosensor arrays for detecting NO release and changes in O2 consumption and superoxide production via implanted multi-analyte sensor arrays. This offers unique opportunities to study real-time dynamics of cellular behaviour, signalling and metabolism during the early stages of vascular remodelling for the first time and enable elucidation of the interplay between soluble factors and the extracellular matrix, in vivo. The first project will involve exposure of animals to two weeks of hypoxia with subsequent haemodynamic analysis and implantation of multi-analyte sensor arrays (MacLean lab). The second project would involve the Cooper lab to record, interpret and produce predictive response models.

Prof Andy Baker and Dr Richard Burchmore

The use of viruses as therapeutic agents in "gene therapy" holds promise for many clinical applications yet presents unique safety implications for patients. A principal component of assessing utility and risk in to understand in great depth the basic aspects of virus:host interactions that govern such processes. Array approaches will be used for assessing the influence of virus infection on the transcriptional and proteome programming and novel in vivo imaging approaches using quantum dot labelled viruses and imaging in vivo. Collectively, these studies will underpin the potential benefits and risks associated with the use of these viruses in translational and clinical applications. The student will carry out the first project in the Baker lab to carry out the in vivo infection studies and subsequent physiological measurements of blood pressures and cardiac function. The second will be carried out in the Pitt lab to apply transcriptional and proteomic systems approaches.

Prof Hugh Willison (in vivo) and Dr Richard Burchmore (systems)

Correlating binding behaviour of protein-glycan interactions in artificial membranes with their biological effects in vivo. We have developed combinatorial glycoarray platforms to observe protein interactions with diverse species of glycans in complexes with each other and with related membrane lipids. This methodology allows us to visualise enhancing and attentuating protein-glycan interactions that might have biological counterparts in living membrane systems. The biological relevance of interaction data derived from glycomicplatforms needs to be validated in living organisms in which the topological organisation of glycan-bearing plasma membranes is fluidic, being subject to constant reorganisation through recycling and lateral diffusion. Students will choose targets glycans and their protein binding partners to assess the relationships between array-derived and organism-derived data.

In the in vivo project antibodies (Willison) will be administered to different live neuromuscular preparations in anaesthetised mice, or following IP injection would dissect out the tissues, and look for binding by microscopy. These mice are transgenic for difffern patterns of ganglioside expression. They would then correlate this with in vitro binding behaviour on microrarrays (Pitt).

Prof Godfrey Smith and Dr Colin Berry

Our research focus is acute myocardial infarction which is a leading global cause of premature illness and death.1 We use magnetic resonance imaging (MRI) in our research since it is highly informative for heart function and injury. Pre-clinical studies using cardiac MRI in animal models provide useful information which may not be possible to obtain clinically. The BHF Glasgow Cardiovascular Research Centre has recently established a state-of-the art 3.0 Tesla MRI facility.2We are undertaking translational research with MRI and mathematical models to better understand the pathophysiology of adverse remodelling after acute myocardial infarction (MI).This translational approach means that we study the research problem using standardised methods which can be used in a similar way from experimental studies through to downstream clinical studies. Ultimately, the use of the same MRI methods in animal models and patients will help provide clinically-relevant results. In this MRes project, we will focus on imaging the rabbit heart. This model is well established in our Centre (Professor Godfrey Smith’s group3). Our MRI team have recent experience of rabbit heart imaging at 3.0 Tesla (in vivo and ex vivo). Furthermore, both teams currently collaborate with Professor Luo4 and Hill in the Mathematical Biology Group. This study will bring together these groups in order to image and model the healthy rabbit heart in vivo. MRI methods will involve trueFISP cine for mass and function. Computer methods will potentially involve non-linear techniques and finite element modelling. The student will be supervised and supported throughout the project in order to achieve learning and development objectives. The first objective is to develop and optimise survival imaging in the rabbit, using a team-based approach to identify problems and solutions. The second objective is to provide cardiac MRI data which will be useful for mathematical modelling. These are key methodological steps which would set the scene for the next stage, which would be survival imaging before and after experimental MI. Paired MRI data would then be used to study mathematically the affects of acute injury on heart structure and function.

Prof Rainer Breitling and Prof Mike Barrett

Kinetic models of metabolism are powerful tools of systems biology. They typically use a single set of enzymatic parameters, chosen by the modeler; this approach has difficulties accounting for the unavoidable uncertainty associated with biological experiments and incomplete knowledge. In this project, we want to address this issue by developing a new type of kinetic model, which explicitly incorporates uncertainty in a statistically principled manner, using trypanosome metabolism as our test case. This project will be centred in making computer-based predictions on parameter ranges of individual enzymes that can explain whole model outputs. A detailed classical model is available as a starting point. Selected parameters that turn out to be particularly influential for predicted parasite biology will be quantified and updated based on targeted experimentation.

Prof Mike Barrett and Prof Rainer Breitling

Trypanosomes cause the disease sleeping sickness. These parasites have an intriguing metabolism whereby they compartmentalize many of the early steps of glycolysis witin an organelle, the glycosome. It appears that compartmentalization allows them to regulate glucose metabolism by carefully balancing phosphate and redox balance within the organelle. This project proposes to determine the rate at which ribose 5-phosphate and ribose accumulate within trypanosomes in wild type cells and also cells in which the ribokinase enzyme is down regulated. State of the art laboratory-based metabolomic analysis taking measurements in time series will describe the rates at which these metabolites interconvert. The data will be added to dynamic models of trypanosome metabolism as iterative rounds of model building aim to reproduce laboratory observations.

Dr John Riddell and Dr Richard Burchmore

Injuries to the spinal cord vary in severity and in some cases there can be significant recovery of function over time and certain individuals respond well to intense rehabilitative strategies. The aim of this project is to identify biomarkers that can predict, at an early stage after injury 1) the severity of the injury 2) the likely degree of spontaneous recovery and 3) those likely to respond to rehabilitative strategies. This will initially be investigated in rodent models of spinal contusion injuries. A force feedback impactor device will be used to set up batches of animals with highly reproducible injuries of graded severity. Cerebrospinal fluid and/or serum will be collected from these animals at different time-points and subjected to appropriate proteomic analysis (e.g. HPLC or MALDI techniques) to identify constituents that are elevated following spinal cord injury and their correlation with injury severity. The eventual aim is to examine the same proteins in cerebrospinal fluid from human spinal cord injured patients to determine how well they predict injury severity and extent of recovery.

Dr Simon Kennedy and Dr Ian Salt.

AMP-activated protein kinase (AMPK) is a key enzyme, present in vascular tissue which regulates cellular and whole-body metabolism. We and others have proposed that AMPK has beneficial anti-atherosclerotic effects, reducing arterial cell inflammation and the accumulation and damaging effects of lipids in the artery wall. We have recently shown that AMPK activation relaxes arteries, an effect that is reduced in mice with atherosclerosis, yet we do not know how AMPK contributes to the development of cardiovascular disease. We will investigate this in animal models, including a rat model of hypertension and in human arteries and veins from normal and diabetic patients. The study will utilise in vivo techniques as well as blood vessel function studies and cellular approaches to study AMPK expression and phosphorylation and the pathways involved in AMPK regulation under experimental conditions. The project will help to better understand how AMPK is regulated in disease and provide evidence of whether AMPK is a viable therapeutic target in cardiovascular disease.

Applications (CV, career intent statement, two references and support letter from Head of Department) should be emailed to the MVLS Graduate School, c/o Catherine Turnbull (Catherine.Turnbull@glasgow.ac.uk) and clearly labelled ‘Masters in IMB/Systems Biology’. Informal enquiries can be directed to Dr. John Riddell (john.riddell@glasgow.ac.uk).

Applications for entry in September 2012 will be considered from March and the deadline for applications will be the end of June 2012 or sooner, if all places have been filled with suitable applicants.