1. The role of G protein-coupled receptors in the physiological processes underlying cognition, memory & mood

Supervisor: Dr James Hislop

My lab focusses on the molecular pharmacology of G-Protein-coupled receptors, and in particular how the regulation of these receptors influences physiology. Of particular interest are those receptors involved in cognition, memory and mood.  We will be using biochemical, and microscopy and fluorescence-based assays to measure the intracellular signalling response of these receptors following addition of different pharmacological agents, and how mutations in these receptors change the function of the receptors.

 

2. The molecular mechanisms involved in wound healing

Supervisor: Dr Dawn Thompson

My lab focusses on the formyl peptide receptors (FPR1, 2 and 3) which are members of the G protein-coupled receptor (GPCR) superfamily and important mediators of the innate immune response. In particular, the FPR2 has been identified as critical in the switch from pro- inflammatory to pro-resolution signalling to initiate tissue healing. However, the precise molecular mechanism(s) involved are yet to be fully elucidated. We will use biochemical (Western Blotting), genetic (qPCR) and microscopic (Flow cytometry and microscopy) techniques to investigate these processes in an attempt to identify new targets for the development of future novel therapeutics.

 

3. Screening teratogens to identify mechanisms of action

Supervisor: Professor Neil Vargesson

My group is interested in how drugs like thalidomide cause birth defects. Using a range of vertebrate embryos we screen drugs and look at resulting molecular changes to identify targets for further analyses. We also screen analogs of thalidomide to identify those with clinically relevant actions without the ability to cause birth defects.

Students should have a background in developmental biology, though a background in pharmacology or biology and an interest in biomedical research will also be fine.

 

4. Assessment of various experimental protocols during assessment of exercise intensity and lactate metabolism

Supervisor: Dr Derek Ball

This lab-based project will examine exercise intensity and lactate metabolism. We have access to some local cyclists who have expressed a desire to take part in formal testing.  Students will participate in management and operation of testing protocols and analyse data that will be of use to the cyclists volunteering for the project. All testing will be done in the dedicated sport science laboratory so students will receive close supervision.

 

5. Heads or tails? Stem cell programming using electrical cues

Supervisor: Dr Ann Rajnicek

The ability to regenerate missing tissues (limbs, central nervous system) spontaneously is limited in humans. However, some animals regenerate tissues naturally by recruiting stem cells to replace missing structures with astonishing accuracy. This project will use a planaria flatworm model to decipher the cues that drive stem cell fate during spontaneous regeneration. These small (~4mm), aquatic, non-parasitic worms regrow a new head (and brain!) within a week after spontaneous fission (during asexual reproduction) or following surgical amputation. This project will explore how natural or applied voltage gradients inside the worm influence stem cell behaviour and regeneration.  Using fluorescence microscopy, cell culture and pharmacological inhibitors we will test the hypothesis that membrane potential and voltage-gated ion channel activity drive stem cell fate. The resulting data may inform future stem cell-based electro-therapies for conditions including brain and spinal cord repair and for chronic wounds (diabetic ulcers, bed sores).

Suitable for 1 or two students. All training will be provided, assuming no prior experience, but basic knowledge of cell biology would be useful.

 

6. Identifying new drug targets for aortic valve stenosis

Supervisor: Professor Graeme F. Nixon

The aortic valve regulates blood flow from the heart to the arteries.  It performs this essential function with every cardiac contraction.  As lifespan has increased in the past few decades, there is an increasing incidence of aortic valve stenosis (AVS).  AVS is characterised by calcification of the valve often requiring invasive surgery for valve replacement.  Failure to treat AVS is lethal and no drug treatments are currently available.  We are investigating new drug targets for AVS by examining the cells which constitute the aortic valve.  Using cell culture from human aortic valves (derived from patients undergoing valve replacement), this project will investigate possible drugs which may be beneficial in AVS.

 

7. Understanding the role of inflammation in Type 2 diabetes and atherosclerosis

Supervisor: Professor Delibegovic

Work in the Delibegovic laboratory is focused on understanding the role of inflammation in Type 2 diabetes and atherosclerosis. As such, we use model organisms as well as primary cells and cell lines to understand the aetiology of these diseases.

 In our summer projects, the students would learn how to isolate, culture and differentiate bone marrow derived macrophages. These would then be stimulated with pro-inflammatory stimuli (normally found upregulated in states of obesity or inflammation) and treated with a number of inhibitors, currently in clinical trials for diabetes or other conditions (repurposing drugs). 

Students would learn cell culture, protein and/or RNA extraction, Western blotting, qPCR, ELISAs and statistical analysis of data. They would also present their data once a week at the lab meeting giving them presentation and communication skills. Students would also be integrated into our Aberdeen Cardiovascular and Diabetes Centre giving them exposure to wider research and networks.

 

8. Image processing and image reconstruction techniques to improve the accuracy of the information extracted from Nuclear Medicine images

Supervisor: Professor Andy Welch

Tomographic Nuclear Medicine techniques such as PET and SPECT provide a high-sensitivity, non-invasive method for studying the function of living tissues in-vivo.  Consequently these techniques have proved highly useful for studying a range of disease processes, both in humans and animals. However, the quality of nuclear medicine images is compromised by high levels of statistical noise and by image degrading factors such as attenuation and scatter of gamma rays prior to detection. Our lab develops application-specific image processing and image reconstruction techniques to improve the accuracy of the information extracted from Nuclear Medicine images.

All training will be provided, but students should have good mathematical and programming skills.

 

9. The impact of sex on the expression and function of GPCR drug targets for pulmonary arterial hypertension

Supervisor: Dr Fiona Murray

Pulmonary arterial hypertension, high blood pressure in the lung, is a devastating condition that leads to heart failure. Pulmonary arterial hypertension has no cure. Pulmonary arterial hypertension is associated with a thickening in the walls of the blood vessels in the lung, which blocks the flow of blood. Female bias of pulmonary arterial hypertension (ratio of 4:1, female vs. male) and differential response to drugs is known, however many researchers fail to consider sex in biomedical research. Decreased levels of a chemical mediator that relaxes the pulmonary artery, namely cAMP, is associated with the progression of pulmonary arterial hypertension; G protein-coupled receptors (GPCRs) are drug targets to increase cAMP. This project aims to investigate the impact of sex on the expression and function of GPCR drug targets for pulmonary arterial hypertension in order the advance the understanding of the disease and to uncover novel clinically relevant drug targets.

 

10. Study of a new receptor target for brain and spinal cord disease

Supervisor: Professor Peter McCaffery

RARs are the receptors for retinoic acid and have powerful actions to regulate cell growth and survival via their control of gene expression. Retinoic acid was one of the first “precision” treatments for cancer, targeting the chromosomal translocation of the retinoic acid receptor gene in acute promyelocytic leukemia. RAR ligands are also used to treat a variety of skin diseases. New discoveries though suggest that RAR ligands have far more wide-ranging effects and may be effective for diseases of the central nervous system.  This action is through a polypharmacological effect promoting not just neuronal survival through actions on gene expression and kinase activity, but also through anti-inflammatory properties and enhancing neuroplasticity to improve learning and memory functions of the brain. Not enough though is known about the molecular action of RAR ligands on the individual neuron, which could open an entirely new field. The project will study the action of RAR ligands on motor neuron derived cells placed under stress to mimic disease and investigation of the ways in which the RAR ligands may protect the cells.

Students should have a background in biochemistry or cell biology and should be in either their third or fourth year of study.

 

11. Stem cells in development and maintenance of the eye.

Supervisor: Professor Martin Collinson

Good vision is often considered essential for normal life, yet millions of people experience visual problems, even blindness, due to failure of eye development or postnatal maintenance. We are interested in problems with eye growth leading to microphthalmia or refractive errors such as short-sightedness, and  visual problems arising from breakdown of the cornea.  This project will investigate the genes controlling proper stem cell activity of the eye, in particular those required for the transparent anterior eye structures, the lens and the cornea.  The project will include the creation and analysis of genetic mutations in eye tissues, alongside assays for stem cell activity and the phenotypic analysis of mice carrying genetic defects that may compromise the stem cells, using standard histological and molecular biology techniques.  

 

12. Antimicrobial resistance-driven changes in microbe-host interactions

Professor Carol Munro and Dr. Delma Childers

Antimicrobial resistance (AMR) is a major clinical concern in the treatment of patients infected with microbial pathogens. We are investigating AMR in two major human fungal pathogens, Candida albicans and Candida glabrata, and how AMR contributes to adaptation to stress and evasion of human immune responses by these species. The aims of this project include characterising changes in stress phenotypes, innate immune sensing of fungal cells, and identifying the molecular determinants that link antimicrobial resistance with these other virulence-relevant traits. Students will be trained in molecular, microbiological, and cell biology approaches for this project. Students will also receive training in science communication by participating in Aberdeen Fungal Group lab meetings.

Students should have a background in biology and an interest in microbiology and molecular biology.

 

13. Focussed on Fat: Understanding the function of genes control human adipose tissue development and how they influence metabolic health.

Supervisor: Dr Justin Rochford, Rowett Institute, University of Aberdeen.

Adipose (or fat) tissue acts as a crucial safe store for lipids in the body. This is starkly demonstrated by rare individuals with a condition called Congenital Generalised Lipodystrophy, who are essentially unable to make adipose tissue. Because they have no normal adipose stores, lipids instead accumulate in other tissues causing severe diabetes and cardiovascular disease. This also occurs in common obesity where adipose stores can become overfilled, causing lipids to overflow into other tissues. Hence, studying what happens in lipodystrophy can not only identify new treatments for this serious condition, but can also lead to a better understanding of diseases associated with obesity. Congenital Generalised Lipodystrophy is most often caused by mutations in either the AGPAT2 or BSCL2 genes. Our lab investigates how AGPAT2 and BSCL2 regulate fat development and why mutations in these genes cause lipodystrophy and diabetes. We have previously shown that the proteins produced by these genes, called AGPAT2 and seipin respectively, physically interact. However, exactly how these proteins regulate adipocyte development is not known. Our aim is define precisely how these critical regulators of human adipose tissue development perform this role, understand how their loss causes severe metabolic disease and uncover novel potential therapies for patients with lipodystrophy.

 

14. Finding novel anticancer agents from plants

Supervisor: Prof Heather Wallace

Many of our current anticancer drugs are derived from plant sources.  For example, etoposide used in the treatment of multiple cancers is derived from the mandrake root and the vinca alkyloids are derived from the periwinkle plant.   This study, which is part of a larger project, aims to investigate the potential of a range of natural products to inhibit the growth of human cancer cells.  Up to 5 natural products will be tested and they will be ranked in order of efficacy. Ultimately, this project aims is to link the success of each product to the molecular signature of the cancer cell in order to try to find a response signature that might help in treatment choices.