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Dr R Jarvis 
Function studies of the Arabidopsis Tic Complex 

£200,636 BBSRC
Chloroplasts are organelles within plant cells that carry out the reactions of photosynthesis. Like mitochondria, they are descendent from a free-living prokaryotic organism that entered the eukaryotic lineage through endosymbiosis. Today, >90% of chloroplast proteins are encoded in the cell nucleus, synthesized on cytosolic ribosomes, and imported into chloroplasts by translocon complexes in the outer and inner envelope membranes (Toc and Tic, respectively). Protein translocation through the Toc/Tic import apparatus consumes large quantities of ATP in the chloroplast interior. It is assumed that this ATP requirement is attributable to the molecular 'motor' that drives chloroplast protein import. To elucidate the composition of this motor, we isolated Arabidopsis knockout mutants lacking three key components of the Tic complex. We will characterize the phenotypes of these mutants in detail in order to determine whether the affected Tic components play roles in the chloroplast protein import motor.

Dr C Dart 
A-kinase anchoring proteins and PKA signalling to arterial Katp channels 

£169,419 British Heart Foundation 
The diameter of arteries changes to match blood flow to tissue demands for oxygen and energy. The degree of arterial dilation is regulated by specialized proteins found in the membranes of the cells that make up the artery. One of these proteins, the ATP-sensitive potassium (KATP) channel, is particularly important and forms the target for therapeutic drugs designed to combat angina and high blood pressure. To function normally, arterial KATP channels rely on interactions with a network of other proteins. This project aims to learn more about the protein infrastructure that surrounds KATP channels (particularly the role played by so-called ‘anchoring’ or ‘scaffold’ proteins) and how it affects the way KATP channels work. We hope that our results will not only give fundamental information about the cellular mechanisms that control KATP channels, but may ultimately also offer new targets for the development of better treatments for diseases of the circulation.

Dr E Raven 
Defining substrate specificity in ascorbate peroxidase 

£207,908 BBSRC 
We seek a complete rationalisation of the substrate binding specificity in ascorbate peroxidase (APX). The experimental approach uses a combination of transient (pre-steady state) and steady state kinetic techniques, and protein engineering methods. APX is an excellent model for probing these questions since its substrate binding properties are diverse and place it at the interface between the class I and class III haem peroxidases. The specific aims are: (i) to probe binding of ascorbate at the gamma-meso haem position, (ii) to identify the location of the second ascorbate binding site in APX, (iii) to examine the role of hydrophobic interactions in determining aromatic substrate binding affinity and (iv) to engineer a cytochrome c binding site into APX. We will use this information to provide more detailed rationalisation the different functional activities and substrate binding specificities exhibited by the class I and class III haem peroxidase enzymes. 

Dr P Jenkins
Develop a less toxic analogue of fascaplsin as a novel therapeutic agent for the treatment of cancer
£35,333 Cancer Research UK via De Montfort University
The natural product fascaplysin initiates the process of apoptosis, controlled cell death, in cancer cells. This action arises because fascaplysin is an inhibitor of the enzyme cyclin dependant kinase Cd k-4 which is essential for cell division. However, fascaplysin is a toxic compound which prevents its use as an anti-cancer drug. The aim of this project is to design and synthesise new anti-cancer compounds based on fascaplysin. The project will involve organic synthesis and molecular modelling under the supervision of Dr P R Jenkins and Dr M J Sutcliffe at the Chemistry Department, University of Leicester and the biological evaluation of the compounds prepared will be carried out in the laboratory of Professor B Chaudhuri of the Department of Pharmacy at De Montfort University. The project will be carried out by two post-doctoral research assistants for three years supported by Cancer Research UK.

Dr M Cooke 
Determination of maternal caffeine intakes associated 
with increased risk to the fetus 

£382,922 Food Standards Agency 
Tea, coffee, chocolate/cocoa, cola and energy drinks, are major sources of caffeine, and an appreciable number of non-prescription drugs may also contribute significantly. Increasingly, caffeine intake during pregnancy has been associated with malformation, low birth weight or spontaneous abortion and consumption of caffeine is common during pregnancy. Whilst a significant number of epidemiological studies suggest a negative effect of caffeine upon pregnancy i.e. increased incidence of miscarriage and low birth weight, there is little empirical data to support these findings. Our international consortium, in collaboration with the University of Leeds, will undertake a study of 3000 pregnancies. Birth weight assessments, questionnaires, blood analysis and genetic studies will all be performed to determine the relationship between maternal caffeine intake and risk to the fetus. These results will allow the Food Standards Agency to provide guidance to pregnant women and hence reduce risk and anxiety amongst these women.

Dr S Redsell 
Nurses' and general practitioners' consultations: patients' expectations for same day minor illness appointments 

£13,628 Royal College of General Practitioners
Several recent studies have shown that patients are more satisfied with nurse consultations than with general practitioner consultations. This study will explore patient’s accounts of their expectations of care in nurse and general practitioner consultations. This will allow us to assess whether there are underlying differences in patients’ expectations of nurse and general practitioner consultations, which might explain the difference in reported satisfaction rates. The findings would assist in the interpretation of trials that have shown higher levels of satisfaction with nurse consultations among patients with minor illness and enable practices to make better informed decisions about the role of nurse practitioners.

Professor L Unwin
Department of Trade and Industry
Finding ways to improve workforce development is high on the agenda of the UK government, the trade unions, and organisations concerned with ensuring employees have access to learning opportunities. The Centre for Labour Market Studies will explore a range of issues related to workplace learning in its new project funded by the Department of Trade and Industry. The project will pay particular attention to the impact of 'informal' workplace learning (as opposed to formal training courses) on business productivity. 
Resulting from the project will be a series of case studies illustrating how employers might support and make better use of informal learning practices. Work will also be carried out to develop and test a major DTI employer survey to provide evidence for such bodies as the Sector Skills Councils, the Learning and Skills Council and the Regional Development Agencies. 

Professor C Graham 
Review of the goals, structure and effectiveness of RPC network's work with train companies 
£14,700 Rail Passengers Council
The Rail Passengers Council has contracted with the University’s Centre for Utility Consumer Law to review the way its regional committees collaborate in speaking up for passengers. The railways run throughout the country, and across Rail Passenger Committee boundaries. The Rail Passengers Council wants to make sure its regional committees work together effectively in pushing for better services for rail passengers.
The review is led by Cosmo Graham, Director of the Centre for Utility Consumer Law, and Professor of Law at the University. He commented, “I am delighted my Centre and the University have been invited to advise the railways consumer body. Rail travel is well short of what passengers want at the moment, and we are confident that my Centre’s experience of consumer representation in the public utilities will assist us in offering helpful advice to the Rail Passengers Council.

Anders Hansen
The status of teachers: Media and public images of teachers and the teaching profession
£130,156 DfES
The mass media are an important source of images and definitions regarding the education system, the status of teachers and the teaching profession. As part of a larger investigation with colleagues at the University of Cambridge into the Status of Teachers, this research project will examine the role played by the media in the creation of public definitions and understanding of teachers and the teaching profession. Focusing on analysis of media coverage and media professionals, the study will show: the dominant images/definitions of the teaching profession portrayed in the media and changes in such definitions during the last decade; the values, characteristics, status, challenges and rewards associated with teaching and emphasised in media reporting; who the key organisations, individuals and public political figures contributing to the public definition of the teaching profession are; and the roles and practices of journalists and other media professionals in the creation and communication of public definitions of teachers.

Professor A Gesher 
Phase-1, single- and multiple-dose safety and pharmacokinetic clinical study of resveratrol - year 1 of 2 

£280,355 NCI via University of Michigan
Resveratrol is a substance found in plant-derived foods such as peanuts and red grapes. There is evidence from biochemical experiments and animal experiments that resveratrol exerts activities which may help delay or prevent the onset of cancer.
Nobody knows really how resveratrol at low or high doses is absorbed, distributed and excreted when given to humans, and how much can be found at organ sites in which it is thought to prevent cancer. The National Cancer Institute commissioned a study in Leicester together with the University of Michigan in which we shall administer resveratrol to human volunteers and study its disposition in the body. We shall also explore if resveratrol causes biochemical changes in blood components which reflect its pharmacological efficacy. The results will help to optimise the design of proper long-term clinical trials of resveratrol as cancer chemopreventive agent.

Professor W Harper 
Supplement - Hip fracture outcome 

£35,346 University Hospital Leicester 
Hip fractures are a common problem which affects many elderly people. The University Department of Orthopaedic Surgery has an ongoing project of research to improve the outcome of hip fractures. The present Research Fellow, Mr Mehool Acharya, will be looking at causes of confusion postoperatively, and ways of reducing this. Mr Acharya has a particular interest in injury to the brain and measuring blood markers for brain injury.

Dr C Pole
New consumers? Children, fashion and consumption
£110,782 ESRC
This two year project funded by ESRC at £110,781 examines children's clothing consumption. A sample of 6-11 year olds and their families, differentiated by key social variables, will be studied for a calendar year. Interviews will also be held with children’s wear industry executives. Children's active consumption of fashion will thus be studied in the context of both 'push' (design, marketing) and 'pull' (pleasure, desire) factors.

Mr R Sayer
Investigation of interleukin-10 and other cytokines in the pathogenesis of aortic aneurysms
£37,500 University Hospitals of Leicester R&D
Abdominal aortic aneurysms are swellings of the main blood vessel inside the abdomen. As they increase in size the risk of bursting increases. The cause of these swellings remains unknown but it is possible that they are caused by chemicals in the blood (cytokines) that control the response to inflammation. This project investigates the role of these chemicals in the wall of aortic aneurysms.

February 2003

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