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Dr D Heery
Structure/function analysis of the leukemogenic fusion protein MOZ-TIF2 and the wild type MOZ protein (year 2)

£38,781 Cancer Research UK
Acute Myeloid Leukemia (type M4/M5) is characterised by gene translocations resulting in fusion of the histone acetyltransferase MOZ (monocytic leukemia zinc finger protein) to CBP (CREB Binding protein), p300 and more rarely, the adaptor protein TIF2. CBP and p300 are function as global coactivators, whereas TIF2 is a Nuclear Receptor-specific cofactor that recruits CBP/p300. CBP and p300 have roles in cell proliferation, differentiation and apoptosis, and CBP is required for normal haematopoiesis. It is not known how the MOZ-TIF2 protein contributes to AML, but it seems likely that it responds inappropriately to the histone code, resulting in aberrant regulation of gene expression networks. This project will investigate the subcellular distribution of the MOZ-TIF2 protein ands its effect on expression of genes regulated by Nuclear Receptors and other factors important in haematopoiesis. This research program will shed light on the role of fusion proteins in AML (M4/M5 and potentially provide model systems to facilitate the development of small molecule therapies.   
mber 2002

Dr A Fry
Investigating the roles of C-Nap1 and Nek2 in centrosome organisation

£173,079 Wellcome Trust
Cell division is an essential biological process for the propagation of unicellular organisms and the growth and reproduction of multicellular organisms such as humans. However, failure to properly control cell division can have disastrous consequences and lead to a range of hyperproliferative disorders including cancer. Our laboratory is working on the biochemical and cell biological processes that underpin cell division. This grant award will enable us to investigate the particular contribution of two important, yet poorly studied proteins, Nek2 and C-Nap1, to the cell division process. In particular, we will address their respective roles in the organization of the centrosome, a critical subcellular organelle that is required for the division of duplicated chromosomes. Results from this basic research will indicate the potential of these proteins as novel cancer therapy targets.
November 2002

Dr N Chong
The pinealocyte and melatonin synthesis: a clock-output and clock-input model system

£178,296   BBSRC
Virtually all biological systems exhibit circadian (~ 24 hours) rhythms. Thus sleep-wake cycles, heart beat, blood pressure, body temperature, and the secretion of many hormones fluctuate during the day in an orderly fashion. Circadian rhythms are the overt consequences of biological clocks – internal timing systems acting within cells. The most highly conserved circadian rhythm in animals is the night-time secretion of the hormone melatonin from the pineal gland, giving an organism a circulating, chemical signal containing information about the time of day. The present study, funded by the BBSRC, will examine the regulation of the enzyme that controls the synthesis of melatonin, using molecular and cellular approaches. Understanding of the molecular, cellular and systems level mechanisms that generate and co-ordinate circadian timing will have enormous impact on our appreciation of health and disease.
September 2002

Dr S Rodrigo

Sarcolemmal Katp channels, oxygen free radicals and functional recovery after metabolic stress in cardiac muscle

£156,182   British Heart Foundation
Cessation of blood flow to parts of the heart, as in a heart attack, damages heart muscle. Intrinsic mechanisms triggered by brief periods of poor blood flow protect the heart against longer events, reducing the death of heart cells and improving the recovery of function. Protection involves energy-sensitive proteins called KATP channels. This project will apply sophisticated techniques to single heart cells to investigate the way in which these proteins are activated, and the way in which their activation leads to protection. The findings should aid clinical treatment and have the potential for future drug development.
October 2002

Dr D Iordanova
Balkan Cinema: Film and History
£98,346  AHRB
Balkan Cinema: Film and History. This four year project is funded by AHRB (£98,450) will allow Dr. Dina Iordanova of the History of Art/Film Studies department to expand her work in the cinema of the Balkan nations (Greece, former Yugoslavia, Bulgaria, Romania and Albania). The poroject will employ a post-doctoral researcher. It also has a funded PhD studentship attached. The work on the project will lead to scholarly publications that will highlight the cinematic heritage of this lesser-known part of the European continent. The focus of research will be on the specific correlation of cinematic narrative and historical discourse and will continue work which Dr. Iordanova has already started with the monographs 'Cinema of Flames: Balkan Film, Culture and the Media' (BFI< 2001) and 'Emir Kusturica' (BFI, 2002).
June 2002

Dr E Raven
A new biological mass spectrometry facility for the centre for chemical biology - Research Equipment Initiative 2002

£150,448 BBSRC
This grant, headed by the Departments of Chemistry and Biochemistry, will fund a new, high throughput, biological mass spectrometry facility for the Centre for Chemical Biology. This facility will play an essential part in the development of Chemical Biology in the 'post-genomic' era in Leicester by making it possible for us to take advantage of the speed and sensitivity of modern mass spectrometry in proteomics, in chemogenomics and in supporting structural biology, combinatorial chemistry, and the development of novel biocatalysts. The application involves a number of major projects within three major themes of Proteomics, Molecular Engineering of Proteins, and Combinatorial Chemistry and Chemogenomics. 
November 2002

Dr P Monks
Intercontinental transport of ozone and precursors (ITOP)

£31,829 NERC
It has become increasingly clear in recent years that surface level emissions and resulting photochemical pollution may no longer be considered only in the context of local air quality, but that it has potential to be transported on both regional and continental scales. The long-range transport of primary anthropogenic emissions of NOx and volatile organic compound may lead to increases in free tropospheric concentrations of radiatively active species such as ozone and aerosols. A large international experiment is planned for 2004 with aircraft from NASA, NOAA and the UK BAe-146. The NASA experiment will make intensive studies of the outflow of pollutants from N America close to the East coast and the NOAA AESOP experiments will study both air quality and transport of pollution from the Northeast USA.  The UK component (ITOP) aims to perform a co-ordinated measurement and modelling study to better understand the intercontinental transport and transformation of photochemical pollutants during its transit across the Atlantic towards Europe.  The University of Leicester team will be involved making measurements of short-lived chemical species on the UK aircraft as well as analysing the data to investigate the role of the chemistry in making ozone in the long-range transported air masses.
November 2002

Dr A Ellis 
Freezing chemical reactions: trapping intermediates in helium nanodroplets

£437,246 EPSRC   
Helium nanodroplets possess remarkable properties.  They are tiny droplets of superfluid liquid helium generated in the gas phase, each being composed of tens of thousands of helium atoms.  Molecules can be readily dissolved in these liquid droplets and the solutes are mobile in the solution despite the fact that the temperature is exceedingly low, close to absolute zero (-273 °C).  This project will employ these nanodroplets as a unique, ultra-low temperature nano-laboratory.  There are many extraordinary and exciting possibilities.  Our primary aim is to study chemical reactions, to learn how individual molecules approach and react.  Molecules trapped in helium nanodroplets, even highly reactive species such as free radicals, can be ‘frozen’ at the threshold of reaction.  A high intensity laser beam will probe the nanodroplets and provide a uniquely detailed picture of the onset of chemical reactions.     
November 2002

Dr C Beardsmore
Supplement - Respiratory function in infants following ECMO

£12,500   Eastern Leicester Primary Care Trust
This supplementary award will enable us to continue the follow-up of infants who receive Extra-Corporeal Membrane Oxygenation (ECMO) for severe lung disease. Almost all these infants are born at term but suffer from severe but potentially reversible lung disease. ECMO is a treatment that keeps the baby supplied with oxygen while giving the lungs time to rest and recover. Many of the babies have a very good recovery but about half need another hospital admission during the first year of life, usually with a breathing-related problem. Wheezing is fairly common in this group. We see the babies at just over one year of age for developmental and respiratory follow-up. Although many of them have normal or near-normal lung function others do not, and we are able to identify those with ongoing breathing problems.
October 2002

Dr M Pont 
A simulator to support the design of X by wire networks  - Devaraj Avayoo (contribution to costs)

£15,000 Pi Technology
Networks of embedded processors have been used for several years in "fly-by-wire" systems in aircraft. There is now increasing interest in the development of "brake-by-wire", "steer-by-wire" and related systems, for use in passenger cars and other road vehicles. Use of such automotive "x-by-wire" networks has the potential to improve safety, vehicle performance and passenger comfort. However, the designers of these networks face the challenge that the resulting systems must operate very reliably, and - at the same time - have minimal maintenance requirements and a low purchase price.
The aim of this research project is to develop a computer simulation which
will support the design of reliable, cost-effective, x-by-wire networks by allowing different network designs to be rapidly assessed, and their features compared, early in the product lifecycle.
November 2002

Professor R Fraser 
Supplement - Funding for Clinical Governance R&D Unit

£155,932 Leicestershire Health / Eastern Leicester Primary Care Trust

The Clinical Governance Research and Development Unit was established in 1999 as the successor to the Eli Lilly National Clinical Audit Centre. The role of the CGRDU is to research and develop effective methods of clinical governance for primary health care and care at the interface between primary and secondary care. CGRDU has an internationally recognised programme to develop evidence based audit protocols which have been widely used by health professionals to improve care. Recently CGRDU has begun to develop national guidelines for the National Institute of Clinical Excellence (NICE). Other research interests include methods to change clinical practice, patient involvement in health care, and monitoring of outcomes, including mortality.
November 2002

Professor R Fraser 
Supplement - Trent Focus - Leicester unit

£31,900 NHS Trent
This grant provides further support to the Trent Focus, which is a consortium of general practice/primary care and nursing departments in Leicester, De Montfort, Sheffield and Nottingham universities. Its remit is to promote research and development in primary care. Capacity building initiatives include advice to individuals and groups, training events, and support to initiators and collaborators in research.
November 2002

Dr A Wilson
New death certification:  a feasibility study

£22,633 The Shipman Enquiry
This is a pre-pilot study to test the feasibility of the new death certification forms proposed by the Shipman Inquiry. A key element of these proposals is the provision of more detail about events around the time of death. For deaths in the community this would involve a discussion with relatives or others present at this time. The new forms will be piloted with a sample of 20 hospital doctors and 20 general practitioners.
November 2002

Professor R Trembath
Functional characterisation of the cellular domain of BMPRII, the type 2 TGFBeta receptor mutated in primary pulmonary hypertension student - Ms v James 

£68,307 British Heart Foundation
Exchange of gas in the lungs requires not only healthy lungs, but a highly developed yet flexible blood supply.  Primary pulmonary hypertension (PPH) is a devastating disorder due to obstruction of the pulmonary arteries.  A significant degree of optimism surrounds the introduction of new and more effective medical treatments, but also the identification of key genetic alterations critical in disease initiation. 

This scientific training proposal will examine the complex effects of mutations in the PPH gene known as BMPR2.  The studentship will seek to capture novel proteins that specifically stick to portions of BMPR-II, necessary in the transduction of signals and required for the maintenance of the pulmonary vasculature.
November 2002

Professor Sir A Jeffreys
Active L1 retrotransposons and the generation of human genetic diversity

£56,183 Wellcome Trust
Human chromosomes are riddled with DNA fragments that have in the past made copies which have jumped to new chromosome locations. One of the most important classes of such "jumping DNA" is a family called L1. Most human L1s are old and no longer able to jump. However young, active L1s can jump around the human genome, sometimes dragging other pieces of DNA with them and sometimes landing inside genes, which may cause disease. These L1s play an important role in remodelling the human genome, but we don’t fully understand how this process works, nor how frequently L1s jump. We aim to solve two key questions. First, how many L1s that can make jumping copies exist in humans? Second, how often do these jumps occur? We will answer these challenging questions using new techniques that enable direct analysis of active L1s, to illuminate the genomic impact of these mobile elements.
November 2002

Dr J Hunton
New K-theoretic techniques for aperiodic order

£124,866   EPSRC
This grant will fund a research assistant to help Hunton in his continued investigations in mathematical crystallography. The project uses ideas from 'K-theory' - one of the most abstract areas of Pure Mathematics - to describe the physics and structure of minerals whose atomic configurations possess only local symmetries. Leicester is one of the key institutions in the world for this type of interaction between pure mathematics, physics and crystallography.
October 2002

Professor P Williams
EACh*ChilD - a European-Asian Challenge to Childhood Diarrhoea: design of a rapid diagnostic test for the most severe forms of childhood diarrhoea for use in peripheral health care centres in developing countries
£177,053 CEC
Diarrhoea affects the very poorest in the global family. WHO reports 2 million deaths from diarrhoea worldwide annually, primarily of children in developing countries. The most severe cases are due to two bacteria, enteropathogenic Escherichia coli (EPEC) and Shigella flexneri, which together account for 20% of diarrhoeal cases but 50% of deaths. However, it is not apparent that children have EPEC infection until diarrhoea has persisted for 14 days, or Shigella infection until blood appears in their stools, by which time they may have suffered irreversible intestinal damage that is usually fatal. The EACh•ChilD project, which is co-ordinated by the University of Leicester, involves partners in Chennai and Vellore in India and in Yogyakarta on the Indonesian island of Java, as well as scientists at the Robert Koch Institute in Wernigerode, Germany.  The objective of the project is to develop a test kit for rapid early detection of EPEC and Shigella so that effective treatment can begin early enough to prevent potentially fatal intestinal damage and children’s lives can be saved – because EACh•ChilD is precious.
November 2002

Dr G Jones
Supplement - PhD Studentship - Gabriela Martinho de Almeida

£7,370 Portuguese Ministry for Science and Technology
Many drugs used in cancer chemotherapy react with genomic DNA promoting the formation of DNA damage, and certain enzymes play an important role in the reactions of these drugs (i.e. metabolic enzymes, DNA repair enzymes, etc). A wide inter-individual variability in the levels and activities of these enzymes exist among humans, and this is thought to be in some part due to genetic polymorphisms and RNA expression levels. Therefore, the possible influence of these genetic features on drug response is an important factor in determining the success of chemotherapy.

We aim to determine if a correlation exists between a certain genotype or level of mRNA expression and higher or lower incidence of DNA damage in a panel of cancer cell lines, and whether this correlates with any aspect of outcome in human studies. Since in several cases chemotherapy fails, this kind of study will help us to understand why, and whether it is related to genetic traits, and to try to avoid failure by giving the most effective drug according to that person's genotype.
November 2002

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