WELCOME

Welcome to the second edition of Highlights. Within this edition we aim to bring you up to date with recent advances made through ICMR research to better understand cardiovascular and metabolic disease, its development, prevention and treatment.Since the first issues of Highlights there have been a number of exciting developments that have enabled the further expansion of the ICMR. This includes a number of new academic appointments increasing our capacity to explore cardiovascular cell biology and physiology, diet genes and car-diometabolic health, and haemostasis and thrombosis. One of our new researcher leaders, Dr Lucia Stefanini is ‘In conversation’ on page 10.

There have been many recent research breakthroughs across the spectrum of our research, and some specific examples, from genetic epidemiology, atherosclerosis, dietary fats to systems biology and innova-tive use of mathematics, are presented on pages 6 – 9.

A particular highlight for us has been the establishment of the ICMR Cardiovascu-lar Imaging Facilities. In order to remain at the ‘cutting-edge’ of research we have expanded dramatically our imaging facili-ties across the spectrum of our research incorporating cell and molecular, animal and human imaging (see pages 4 and 5). This significant development has been made

possible by substantial investment by the British Heart Foundation, the Wolfson Foundation, the Medical Research Council, the Garfield Western Foundation, some generous private donations and the University of Reading.

The Imaging Centre is an important invest-ment in our scientific future. This marks the beginning of a very exciting phase in the development of the ICMR with a substantial number of new academic groups joining us in the next year and the initiation of a process to develop new infrastructure: labo-ratory facilities and human study and clinical facilities, allowing the closer integration of researchers to provide new and innovative insight to the challenge of reducing the burden of cardiovascular disease.

We hope that you enjoy this brief excur-sion into our work. If you are interested in knowing more or even contributing as a volunteer to one of our studies, please do refer to our website and contact us directly.

The ICMR is a multidisciplinary centre that brings together scientists from a wide range of research fields to work to better understand the causes of cardiovascular diseases and the underlying obesity-related metabolic diseases from which they develop. The activities are broad and wide reaching and this publication aims to give a taster of these activities and examples of our future research directions.

Professor Jon Gibbins

Professor Julie Lovegrove

2 ICMR Highlights | WELCOME

What’s inside? 3 News 4 New IMCR imaging

facility 6 Research highlights 10 In conversation 11 ICMR Travel Award

winners

NEWS | ICMR Highlights 3

NEWS

BREAKTHROUGH: THROMBOSIS – Ś0,1'b7+(�*$3śResearchers within the ICMR have discov-ered that platelets possess specialised pore forming proteins, connexins, which form structures known as hemichannels and gap junctions that allow molecular communi-cation between these cells. Dr Sakthivel Vaiyapuri and colleagues have revealed import functions of these proteins in the control of blood clotting and thrombosis. The results of this study were published in &LUFXODWLRQ and 1DWXUH�&RPPXQLFDWLRQV. Work is ongoing to establish how the func-tions of these proteins in platelets are controlled since connexins may represent new anti-thrombotic drug targets.

BREAKTHROUGH: STATINS – THE CLOT THICKENSStatins are usually used to reduce the amount of cholesterol in our blood circula-tion, but they are also recognised to have FKROHVWHURO�LQGHSHQGHQW�EHQHƬFLDO�HƪHFWV��In a recent study published in the journal %ORRG, Dr Leo Moraes and colleagues dis-covered that some statins reduce platelet reactivity through a mechanism linked to the stimulation of the inhibitory platelet recep-WRU�3(&$0�ƶ��,Q�WKHLU�ZRUN��WKH�HƪHFWV�RI�VWDWLQV�RQ�3(&$0�ƶ�IXQFWLRQ�ZHUH�VKRZQ�WR|LQKLELW�WKURPERVLV�

CHALLENGING DIETARY RECOMMENDATIONS FOR CARDIOVASCULAR 35(9(17,21'DLU\�IRRGV�FRQWULEXWH�WR�D�VLJQLƬFDQW�proportion of dietary saturated fat in the UK diet, yet high milk consumers have a lower cardiovascular disease mortality and W\SH�Ʒ�GLDEHWHV�SUHYDOHQFH��$�KLJK�SURƬOH�research study funded by the MRC aims WR�GHWHUPLQH�WKH�LPSDFW�RI�PRGLƬHG�GDLU\�products produced from low saturated fat/high monounsaturated fat milk on novel and traditional risk factors for cardiovascular disease. See page Ʒ�for details.

IS FIVE-A-DAY ENOUGH? While consumption of fruits and vegetables �)9V��DUH�DVVRFLDWHG�with a lower cardiovascu-lar disease risk, the optimal type and daily intake is unknown, resulting in inconsistent global public health recommendations for F&V intakes. Results from the FLAvanoids 8QLYHUVLW\�RI�5HDGLQJ�6WXG\��)/$9856��VXJJHVW�WKDW�ƬYH�SRUWLRQV�RI�)9�PD\�QRW�be optimum to lower CVD risk, and that ƮDYRQRLG�ULFK�)9V�LQ�SDUWLFXODU�PD\�EH�important in maintaining vascular health (see page Ʒ�IRU|GHWDLOV��

3$9,1*�7+(�:$<�)25�STRUCTURE-DRIVEN VACCINESDr Kim Watson and her group recently solved the structure of MOMP, a major outer membrane protein from &KODPGRSKLOD�SQHXPRQLD, a potential vaccine target for infections leading to cardiovascular events and respiratory diseases.

MOMP shows an occluded barrel, which has

implications for function

+(53(72/2*<�0((76�HAEMATOLOGY …Viper venom proteins exert their enveno-PDWLRQ�HƪHFWV�E\�PDLQO\�DƪHFWLQJ�WKH�cardiovascular system. Researchers at the ICMR have had notable success in exploring WKH�IXQFWLRQV�DQG�HƪHFWV�RI�VSHFLƬF�YHQRP�proteins. By understanding the complex mixtures of active components within

venoms the aim is develop safer and more HƪHFWLYH�PHDVXUHV�WR�WUHDW�WKH�OLIH�WKUHDW-ening symptoms of envenomation. This work and an associated survey of snakebite incidence, mortality and morbidity, has JDLQHG�PHGLD�DWWHQWLRQ�DV�IDU�DƬHOG�DV�WKH�1HZ�<RUN�7LPHV and the 7LPHV�RI�,QGLD.

AWARD FOR ,&05b0(0%(5A scanning electron micrograph of a platelet at an initial stage of activation was published as a cover image in the journal $UWHULRVFOHUR-

VLV��7KURPERVLV��DQG�9DVFXODU�%LRORJ\ in 'HFHPEHU�ƷƵƶƸ��7KLV�image was selected as the 2XWVWDQGLQJ�&RYHU�ƳƱƲƴ�in the ATVB FRQIHUHQFH�LQ�7RURQWR��0D\�ƷƵƶƹ��

NEW EDITORIAL ROLES )25�,&05b$&$'(0,&66L[�QHZ�DSSRLQWPHQWV�EURDGHQ�WKH�,&05pV�role in the publication of high-quality science in a wide range of cardiovascular and meta-bolic research disciplines:

Prof Parveen Yaqoob joined the editorial board of the journal $WKHURVFOHURVLV, Dr Keith Foster joined the Editorial advisory panel of the -RXUQDO &OLQLFDO�6FLHQFH, Dr Gunter Kuhnle is now part of the editorial board of 1XWULWLRQ�DQG�$JLQJ, Dr Jonathan Swan of the editorial board of 0LFURELRPH, Dr Kim Jackson of the Editorial board British Journal of 1XWULWLRQ, and Prof Jon Gibbins joined the editorial Board of the %ULWLVK�-RXUQDO�RI|�3KDUPDFRORJ\.

NEW ICMR IMAGING FACILITYThe last few months has been marked by the launch of our new Imaging Facilities. These state-of-the-art systems will allow us to peer into cells at unparalleled levels of resolution, to look inside human donors and to explore the mechanisms of cardiovascular and metabolic disease in animal models of human disease.

IMAGING CELLS $1'b02/(&8/(6The new ICMR confocal microscopy suite brings cutting edge cellular imaging capabili-ties to Reading. Housed in the Lyle tower, the suite consists of two fully motorised 1LNRQ�$Ư�5�FRQIRFDO�PLFURVFRSHV, each capable of four colour imaging and both equipped with environmental chambers allowing live cell imaging. These micro-scopes support an extremely wide range of G\HV�DQG�ƮXRURSKRUHV�DQG�DUH�DGDSWDEOH��VR�no matter what requirements you have the microscopes should be able to handle it! In DGGLWLRQ�WR�WKLV�ƮH[LELOLW\��HDFK�PLFURVFRSH�also brings its own unique capabilities. One of the systems has been adapted for high speed image acquisition using the fastest scanners and most sensitive detectors available. This will allow users to track very rapid events in cells or to capture images with very low laser power. The other system provides super-resolution imaging capabili-ties. Using a technique called N-STORM images can be captures at much higher resolutions than is possible with standard confocal microscopes with a resolution of ƷƵtƸƵ�QP�DFKLHYDEOH��7KLV�LV�RQH�RI�RQO\�three such systems in the UK and will allow many new novel approaches to investigating the behaviour of cells.

4 ICMR Highlights | NEW ICMR IMAGING FACILITY

IMAGING DISEASE '(9(/230(17Research has shown that body composi-tion is a key component of health and future disease risk. As a result, there is consider-able interest in methods to accurately monitor and assess changes in body com-position. 'XDO�[�UD\�DEVRUSWLRPHWU\��';$��is a non-invasive gold standard technique for the measurement of bone mineral density, an indicator of bone health. The ICMR imaging facilities now include a /XQDU�L';$�ZKLFK�RƪHUV�UHVHDUFK�JUDGH�LPDJH�UHVROX-tion to deliver crisp, high resolution images of the vertebrae.

Historically DXA has only been used to assess bone mineral density. However the Lunar iDXA can also accurately measure total body composition, assessing bone, IDW|DQG�OHDQ�WLVVXH�PDVV�ZLWKLQ�RQH�VKRUW�body scan. Automated software calculates regional percentage body fat and BMD, and the percentage of body fat distributed around the stomach and hips. The soft-ware package, CoreScan, also determines the mass and volume of visceral fat within the abdomen, an indicator of conditions such as the metabolic syndrome and W\SH|,,|�GLDEHWHV��

Mirror imaging software allows scanning of VWXG\�SDUWLFLSDQWV�XS�WR�ƷƵƹ�NJ��ƸƷ�VWRQHV��DQG�ƶ�ƾƸ�P��ƻIW�ƹ�LQFKHV��LQ�KHLJKW��7KH�';$�VFDQQHU�XVHV�D�ORZ�GRVH�RI�LRQLVLQJ��;�UD\��radiation to determine bone, fat and lean tissue mass so this technique is not suitable for use in studies with pregnant women.

%ORRG�YHVVHO��YDVFXODU��G\VIXQFWLRQ�LV�becoming increasingly recognised as an early marker of cardiovascular disease ULVN�DQG�D�FULWLFDO�PRGLƬDEOH�HYHQW�LQ�WKH�development of atherosclerosis. Numer-ous studies have now highlighted the SURJQRVWLF�YDOXH�RI�oLQ�YLYRp�PHDVXUHV�RI�vascular reactivity of both the coronary and peripheral arteries, in predicting future coronary events. The ICMR imaging facili-WLHV�QRZ�LQFOXGHV�WZR�3KLOLSV�&;ƺƵ�SRUWDEOH�ultrasound machines utilising SonoCT imaging technology, each equipped with /ƶƷ�Ƹ�DQG�/ƶƺ�ƼLR�OLQHDU�DUUD\�WUDQVGXFHUV�to provide crisp, high resolution images of the human vasculature. Current applications include the imaging of the diameter of the EUDFKLDO�DUWHU\�XVLQJ�WKH�/ƶƺ�ƼLR�WUDQVGXFHU�to assess nitric oxide mediated vasodila-WLRQ�GXULQJ�WKH�ƮRZ�PHGLDWHG�GLODWDWLRQ�technique and measurement of the carotid intima media thickness.

NEW ICMR IMAGING FACILITY | ICMR Highlights 5

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Intravital microscopyOver the last four years, with support from the MRC, we have established a state-of-the-art intravital microscopy system, which allows the YLVXDOLVDWLRQ�RI�ƫXRUHVFHQFH�VLJQDOV�in vivo. This comprises an upright HSL�ƮXRUHVFHQFH�PLFURVFRSH�ZLWK�D�UDSLG�light source wavelength changer, automated shutter control, automated stage, an image LQWHQVLƬHU�DQG�D�KLJK�VSHHG�GLJLWDO�FDPHUD��This allows simultaneous real-time analysis RI�XS�WR�IRXU�GLƪHUHQW�ƮXRURSKRUHV��DQG�SlideBook software is available to coordinate WKH�FRPSRQHQWV�RI|WKH�V\VWHP��DFTXLUH�GDWD�DQG�IRU�RưLQH�GDWD�DQDO\VLV��

The system has been established within the Haemostasis and Thrombosis Group to study thrombosis, which may be trig-gered using an ablation laser that is directed through the microscope objective lens. The success of this system to measure thrombosis, has led, as part of our recent imaging facility project to the addition of a high speed spinning disk confocal scanner together with multiple laser lines and a high sensitivity camera. This will enable time resolved analysis of thrombus formation in three dimensions allowing the structure and VWDELOLW\�RI|WKURPEL�DQG�FRPSRQHQWV�DQG�processes within to be analysed at levels of

detail that were until recently unimaginable. While initially designed with thrombosis studies in mind, this unique system combin-ing intravital microscopy with high-speed confocal analysis will impact on a wide range RI�,&05|UHVHDUFK��

High frequency ultrasound 9(92|����The 9(92�ưƯƮƮ�is the state of the art system for in vivo imaging studies in rodents and other small species. The system is currently equipped to perform studies of cardiac and vascular function. In addition to the cardiovascular analysis software SDFNDJH��WKH�9(92�ƷƶƵƵ�LQFOXGHV�D�Ƹ'�mode, which allows volumetric analysis of the whole heart or tumours, for quan-WLƬFDWLRQ�DQG�DVVHVVPHQW��DQG�D�JHQHUDO�echography package that allows evaluation of abdominal organs as well as tumours, YHU\�XVHIXO�IRU�H[DPSOH�LQ�WKH�ƬHOG�RI�FDQFHU|UHVHDUFK��

The system has been customised to expand its capabilities through software and hardware upgrade and to evaluate micro YHVVHO�G\QDPLFV��H�J��EORRG�ƮRZ��ZLWK�WKH�use of contrast agents, which is important in disease processes such as cardiac and �YDVFXODU|�GLVRUGHUV��

$ERYH�7KH�1LNRQ�$Ư�5�FRQIRFDO�PLFUR�VFRSH�ZLWK�1�67250�FDSDELOLWLHV��ULJKW��provides dramatically enhanced resolution

compared to conventional optical micro�VFRSHV��OHIW��

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6 ICMR Highlights | RESEARCH HIGHLIGHTS

RESEARCH HIGHLIGHTS

MATHEMATICS, PLFURRNAs AND HEART FAILURE0DUFXV�7LQGDOO�DQG�$QJHOD�&OHUN

A combination of mathematical and cell biological techniques elucidated how miRNAs regulate the expression of ATF3 a major hub in cardiac myocyte response to stress and a potential target for cardiac hypertrophy and heart failure.The function of cells within our bodies is controlled by proteins. Molecules known DV�PHVVHQJHU�51$V��P51$V��FDUU\�WKH�information for protein synthesis from the genes to the ribosomes and allow protein expression. In recent years a new type of 51$V��NQRZQ�DV�PLFUR51$V��PL51$V���KDYH�been discovered and they are thought to be involved in the negative regulation of SURWHLQ|H[SUHVVLRQ��

:RUN�LQ�3URI�$QJHOD�&OHUNpV�JURXS�DW�WKH�ICMR has recently shown that in cardiac P\RF\WHV��KHDUW�FHOOV��WKHUH�LV�D�FOHDU�GLI-ference in the time varying levels of mRNA and protein for a transcriber known as $FWL-YDWLQJ�7UDQVFULSWLRQ�)DFWRU�ƴ��$7)Ƹ�ƶ��$7)Ƹ�is a master regulator of cell response to stress conditions, such as injury, ischemia, ischemia/reperfusion or chemical toxin, and is is known to be important in many disease VWDWHV�LQFOXGLQJ�LQƮDPPDWLRQ��FDQFHU�DQG�cardiovascular disease. Recent studies LGHQWLƬHG�$7)Ƹ�DV�D�QH[XV�LQ�FDUGLRP\RF\WH�hypertrophy as it is required to facilitate the full and proper growth of heart cells. Its SURWHFWLYH�HƪHFW�LQ�SDWKRORJLFDO�K\SHUWUR-SK\�LQ�WKH�KHDUW�VXJJHVWV�WKDW�$7)Ƹ�PD\�EH�DQ�HƪHFWLYH�WKHUDSHXWLF�WDUJHW�IRU�FDUGLDF�hypertrophy and heart failureƷ, thus it is important to uncover the mechanisms that UHJXODWH�$7)Ƹ�H[SUHVVLRQ�DW�WKH�P51$�DQG�the protein level. For this purpose Prof Clerk and Dr Marcus Tindall employed a math-

ematical modelling approach to examine a number of hypothetical scenarios as to how other cellular proteins and transcrib-HUV�PD\�RU�PD\�QRW�LQWHUDFW�ZLWK�$7)Ƹ�'1$�to produce the experimentally observed OHYHOV�RI�$7)Ƹ�P51$�DQG�SURWHLQ��'U�7LQGDOO�developed a series of mathematical models to explore which of these hypotheses may produce results similar to those observed experimentally. Through joint work recently published in the journal 3OR6�&RPSXWDWLRQDO�%LRORJ\�LQ�0D\�ƷƵƶƹƸ, Prof Clerk and Dr Tindall where able to disprove a range of biologically plausible scenarios, some previ-ously considered in the literature, others not. For instance, the reported hypothesis WKDW�WKH�$7)Ƹ�SURWHLQ�PD\�EH�FRQWUROOLQJ�WKH�transcription of its own gene by a negative feedback mechanism was refuted. Among the possible scenarios they postulated the likelihood that miRNAs may be able WR�UHJXODWH�$7)Ƹ�P51$�OHYHOV�E\�ELQGLQJ�and reducing the amount of free mRNA molecules within the cell. Results from the formulated mathematical model were in strong agreement with the experimental data, even under considerable variation in the levels of other proteins in the cell, and strongly suggest that miRNA may work in WKLV�ZD\�WR�FRQWURO�$7)Ƹ�P51$�OHYHOV�QRW�

only in heart cells but also in other cellular systems. Prof Clerk and Dr Tindall are cur-rently considering ways to extend their work to such systems and further understand the role of miRNA regulation.

This research was supported by the %ULWLVK|+HDUW�)RXQGDWLRQ�

Referencesƶ� Giraldo A et al. Feedback regulation by $WIƸ�LQ�WKH�HQGRWKHOLQ�ƶ�UHVSRQVLYH�transcriptome of cardiomyocytes: (JUƶ|LV|D|SULQFLSDO�$WIƸ�WDUJHW��%LRFKHP�-. ƷƵƶƷ�-XQ|ƶ�ƹƹƹ�Ʒ��ƸƹƸtƺƺ�

Ʒ� Zhou H et al. Activating transcription IDFWRU�Ƹ�GHƬFLHQF\�SURPRWHV�FDUGLDF�K\SHUWURSK\��G\VIXQFWLRQ��DQG�ƬEURVLV�induced by pressure overload. 3/R6�2QH. ƷƵƶƶ�ƻ�ƶƵ��HƷƻƼƹƹ��

Ƹ� Tindall MJ & Clerk A. Modelling negative feedback networks for activating WUDQVFULSWLRQ�IDFWRU�Ƹ�SUHGLFWV�D�GRPLQDQW�role for miRNAs in immediate early gene regulation. 3/R6�&RPSXW�%LRO��ƷƵƶƹ�0D\�ƽ�ƶƵ�ƺ��HƶƵƵƸƺƾƼ�

Cardiac myocyte hypertrophy induced by endothe�OLQ�Ư�LV�GLVUXSWHG�LQ�WKH�DEVHQFH�RI�$7)Ʊ��5DW�QHRQDWDO� ventricular myocytes were infected with adenoviruses

�OHIW��RU�DGHQRYLUXVHV�HQFRGLQJ�DQWLVHQVH�$7)Ʊ��ULJKW���WKHQ�H[SRVHG�WR�HQGRWKHOLQ�Ư��ưƲ�K���&HOOV�ZHUH�ƪ[HG�DQG�VWDLQHG�ZLWK�DQWLERGLHV�WR�WURSRQLQ�7�

RESEARCH HIGHLIGHTS | ICMR Highlights 7

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Atherosclerosis is the underlying cause of coronary heart disease and thrombotic strokes and is therefore the leading cause of death in the world. Most cholesterol in plasma is carried in low GHQVLW\�OLSRSURWHLQ��/'/���7KH�R[LGDWLRQ�of LDL (a process caused by free radicals, DQDORJRXV�WR�PLON�EHFRPLQJ�UDQFLG��LV�ZLGHO\�believed to be important in atherosclerosis. The oxidised LDL hypothesis proposes that cells in the arterial wall oxidise LDL LQ|WKH�H[WUDFHOOXODU�VSDFH��LQWHUVWLWLDO�ƮXLG��and then macrophages take it up rapidly, leading to the accumulation of cholesterol in macrophages and the formation of ath-erosclerotic lesions. A problem with this hypothesis is that the oxidation of LDL is inhibited by low concentrations of serum RU|LQWHUVWLWLDO�ƮXLG�DQG�WKDW�ODUJH�FOLQLFDO�WULDOV�have shown no protection by antioxidants DJDLQVW�FDUGLRYDVFXODU|GLVHDVH�

:H�KDYH�VKRZQ�IRU�WKH�ƬUVW�WLPH�WKDW�PDF-rophages oxidise LDL in their lysosomes, rather than, or in addition to, the extracellular ƮXLG��7KLV�UDLVHV�WKH�SRVVLELOLW\�WKDW�O\V-osomes are the major site of LDL oxidation in atherosclerotic lesions. Atherosclerotic OHVLRQV�DUH�LQƮDPPDWRU\�VLWHV�DQG�FRQWDLQ�enzymes, such as sphingomyelinase, that DUH�LQFUHDVHG�LQ�LQƮDPPDWLRQ��:H�SURSRVHG�the hypothesis that LDL is acted on by these HQ]\PHV�LQ�WKH�LQWHUVWLWLDO�ƮXLG�RI�DWKHUR-sclerotic lesions and becomes unstable and aggregates. The aggregated LDL is rapidly endocytosed by macrophages and then oxidised within lysosomes due to the acidic S+��S+�ƹ�ƺ��RI�WKHVH�RUJDQHOOHV�DQG�WKH�presence of redox-active iron inside them. 7KH�O\VRVRPHV�DUH�WKH�ERG\pV�$FKLOOHVp�KHHO�as regards redox-active iron, as they are one

of the very few sites where iron is allowed to become redox active. The evidence to support this hypothesis was obtained using both morphological and biochemi-cal techniques and applied to both mouse macrophages and human blood monocyte-derived macrophages. The iron chelator desferrioxamine, which is pinocytosed by cells and delivered to lysosomes, inhibits LDL oxidation, indicating the importance of iron in the lysosomal oxidation of LDL. The oxidation is also inhibited by chloroquine, a drug that increases the pH of lysosomes, indicating the importance of an acidic pH. The level of oxidation in lysosomes is exten-sive, as shown by the production of ceroid, an advanced oxidation product consisting of oxidised and polymerised lipid-protein complexes. It has been known for many years by pathologists that ceroid is found in cholesterol-laden macrophages in human atherosclerotic lesions. We also showed using spectrophotometry that iron can R[LGLVH�/'/�HƪHFWLYHO\�DW�WKH�O\VRVRPDO�S+|RI�ƹ�ƺ��EXW�QRW�DW�S+�Ƽ�ƹ��

7KHVH�ƬQGLQJV�SURYLGH�D�QRYHO�PHFKDQLVP�to explain how oxidised LDL is formed in atherosclerotic lesions in a sequestered intracellular environment in the presence of seemingly overwhelming antioxidant protection in the extracellular space. It may help to explain why the large clinical WULDOV�RI�DQWLR[LGDQWV�VKRZHG�QR�EHQHƬW�LQ�cardiovascular disease, if the antioxidants FRXOG�QRW�HQWHU�O\VRVRPHV�HƪHFWLYHO\�RU�were consumed in the lysosomes and not replenished. In fact, we have found that vitamin E, the main antioxidant used in

the clinical trials, actually increases, rather than decreases, the initial oxidation of LDL E\�LURQ�DW�DFLGLF�S+��2XU�ƬQGLQJ�SURYLGHV�a rationale for using antioxidants target-ted to lysosomes as a novel therapy for atherosclerosis and we are currently working RQ|WKLV�

/RZ�GHQVLW\�OLSRSURWHLQ��/'/��ZDV�LQFXEDWHG�ZLWK�sphingomyelinase to aggregate it and then incu�bated with macrophages derived from human blood

�WRS�SLFWXUH��RU�KXPDQ�PDFURSKDJH�OLNH�7+3�Ư�FHOOV��ERWWRP�SLFWXUH���7KH�FHOOV�ZHUH�VWDLQHG�ZLWK�D�UHG�G\H��2LO�5HG�2��WR�VKRZ�WKDW�WKH\�KDG�DFFXPXODWHG�OLSLG��PDLQO\�HVWHULƪHG�FKROHVWHURO���ZKLFK�ZDV�FRQ�WDLQHG�ZLWKLQ�O\VRVRPHV�LQ�WKH�FHOOV�

285�),1',1*�3529,'(6�$�5$7,21$/(�)25�86,1*�$17,2;,'$176�7$5*(77('�72�/<62620(6�$6�$�129(/�7+(5$3<�FOR ATHEROSCLEROSIS AND WE ARE &855(17/<�:25.,1*�21b7+,6�

This research was supported by the %ULWLVK�|+HDUW�)RXQGDWLRQ�

Referencesƶ� Wen Y & Leake DS.Low density lipoprotein

undergoes oxidation within lysosomes in cells. &LUF�5HV��ƷƵƵƼ�0D\�ƶƶ�ƶƵƵ�ƾ��ƶƸƸƼtƹƸ�

Ʒ� Satchell L & Leake DS. Oxidation of low-density lipoprotein by iron at lysosomal pH: implications for atherosclerosis. %LRFKHPLVWU\��ƷƵƶƷ�0D\�ƽ�ƺƶ�ƶƽ��ƸƼƻƼtƼƺ�

GENETIC RESEARCH CLARIFIES LINK BETWEEN +<3(57(16,21�$1'�9,7$0,1�'�'(),&,(1&< Findings from the D-CarDia Collaboration9LPDO�.DUDQL

Dr Vimal Karani is a Lecturer in Nutrigenetics at the Department of Food and Nutritional Sciences, University of Reading and an Honorary Lecturer in Genetic Epidemiology at the University College London.The D-CarDia (Vitamin D, Cardiovascular DQG�'LDEHWHV��FROODERUDWLRQ�LQYHVWLJDWHV�the causal relationship between vitamin D levels and the risk of cardiovascular disease-related traits such as obesity, blood pressure, hypertension, diabetes and LQƮDPPDWLRQ��7KH�FDXVDO�UHODWLRQVKLS�KDV�been established using a genetic approach FDOOHG�o0HQGHOLDQ�5DQGRPL]DWLRQp�ZKHUH�the causality is inferred from associations between genetic variants that mimic the LQƮXHQFH�RI�D�PRGLƬDEOH�HQYLURQPHQWDO�H[SRVXUH��H�J��YLWDPLQ�'��DQG�WKH�RXWFRPH�of interest (e.g. cardiovascular disease-UHODWHG�RXWFRPHV�VXFK�DV�K\SHUWHQVLRQ���Because gene variants do not change over time and are inherited randomly, they are not prone to confounding and are free from UHYHUVH|�FDXVDWLRQ��,I�YLWDPLQ�'�FRQFHQWUD-tions are causally involved in determining blood pressure or the risk of hypertension, WKHQ�WKH�JHQHWLF�YDULDQWV�WKDW�DƪHFW�FLU-culating concentrations of vitamin D could EH�H[SHFWHG�WR�DƪHFW�EORRG�SUHVVXUH�DQG�

�K\SHUWHQVLRQ|ULVN��7KLV�DVVXPSWLRQ�ZDV�valid for at least two of the genes that DƪHFW�YLWDPLQ�'��QDPHO\�&<3Ƴ5Ʋ (encod-LQJ�F\WRFKURPH�3ƹƺƵ��IDPLO\�Ʒ��VXEIDPLO\�5��SRO\SHSWLGH�ƶ��DQG�'+&5Ƹ (encoding Ƽ�GHK\GURFKROHVWHURO�UHGXFWDVH���7KHVH�genes function upstream of vitamin D pro-GXFWLRQ�DQG�DƪHFW�YLWDPLQ�'�V\QWKHVLV�RU�substrate availability. Hence, the genetic markers from these two genes were used DV�SUR[\�PDUNHUV�IRU�OLIHORQJ�GLƪHUHQFHV�LQ�vitamin D status to test for a causal associa-tion with blood pressure and hypertension.

7KH�ƬUVW�SXEOLFDWLRQ�IURP�WKH�'�&DU'LD�FRO-ODERUDWLRQ�RQ�ƹƷ�ƵƷƹ�LQGLYLGXDOV�KDG�VKRZQ�that obesity leads to lower vitamin D status ZKLOH�DQ\�HƪHFWV�RI�ORZ�YLWDPLQ�'�VWDWXV�RQ�obesity are likely to be small ƶ. To date, the D-CarDia collaboration comprises nearly ƶƵƽ�ƵƵƵ�LQGLYLGXDOV�IURP�WKH�8.��FHQWUDO�DQG�southern Europe, North America, Scandi-navia and Finland. These data were used for examining the causality between low vitamin D status, blood pressure and hypertension. To further increase the statistical power of the study, the results were meta-analysed �FRPELQLQJ�WKH�UHVXOWV�IURP�GLƪHUHQW�studies in order to identify patterns, sources of disagreement or other interesting rela-WLRQVKLSV�DPRQJ�WKRVH�UHVXOWV��ZLWK�WKH�summary data from the International Con-VRUWLXP�IRU�%ORRG�3UHVVXUH��,&%3���&RKRUWV�for Heart and Aging Research in Genomic (SLGHPLRORJ\��&+$5*(��DQG�*OREDO�%ORRG�3UHVVXUH�*HQHWLFV��*OREDO�%3*HQ��FRQVRUWLD��WRWDO�RI�ƶƺƵ�ƵƵƵ�VXEMHFWV���

In meta-analyses of data from these �FRQVRUWLD��HYHU\�ƶƵ��UHODWLYH�LQFUHPHQW�LQ|JHQHWLFDOO\�LQVWUXPHQWHG�YLWDPLQ�'�FRQ-FHQWUDWLRQ�ZDV�DVVRFLDWHG�ZLWK�Ƶ�Ʒƾ|PP+J�ORZHU�GLDVWROLF�EORRG�SUHVVXUH��3 Ƶ�Ƶƶ���D�

Ƶ�ƸƼ�PP+J�ORZHU|�V\VWROLF�EORRG�SUHVVXUH��3 Ƶ�Ƶƺ��

DQG�DQ�ƽ�ƶ��

UHGXFHG�RGGV�RI�K\SHUWHQVLRQ��3 Ƶ�ƵƵƷ���7KH�HVWLPDWHG�HƪHFW�ZDV�UHODWLYHO\�VWURQJ�for hypertension, with the D-CarDia data VXJJHVWLQJ�ƽ��UHGXFWLRQ�LQ�WKH�ULVN�RI�K\SHUWHQVLRQ�IRU�HDFK�ƶƵ��LQFUHPHQW�in vitamin D concentrations. The results from this Mendelian randomisation study Ʒ provide evidence that increased vitamin D concentrations are causally associated with

reduced blood pressure and hypertension ULVN��)XUWKHUPRUH��WKHVH�ƬQGLQJV�VWUHQJWKHQ�the case for appropriately powered, well-designed randomised clinical trials to investigate the necessary vitamin D doses and appropriate target groups for the pre-vention or treatment of hypertension.

Low vitamin D status is common through-RXW�WKH�ZHVWHUQ�ZRUOG��KHQFH��WKH�SXEOLF�KHDOWK�LPSOLFDWLRQV�RI�WKHVH�ƬQGLQJV�DUH�notable. In view of the costs and side-HƪHFWV�DVVRFLDWHG�ZLWK�DQWLK\SHUWHQVLYH�drugs, the potential to reduce hypertension by vitamin D is very attractive.

8 ICMR Highlights | RESEARCH HIGHLIGHTS

THE RESULTS FROM THIS MENDELIAN RANDOMISATION STUDY ư�3529,'(�EVIDENCE THAT INCREASED VITAMIN D CONCENTRATIONS ARE CAUSALLY ASSOCIATED WITH REDUCED BLOOD 35(6685(�$1'�+<3(57(16,21�5,6.�

Referencesƶ� Vimaleswaran KS et al. Causal Relationship

between Obesity and Vitamin D Status: Bi-Directional Mendelian Randomization Analysis of Multiple Cohorts. 3/R6�0HG. ƷƵƶƸE�ƶƵ��HƶƵƵƶƸƽƸ�

Ʒ� Vimaleswaran KS et al. Association of vitamin D status with arterial blood pressure and hypertension risk: a Mendelian Randomisation study. /DQFHW�'LDEHWHV��(QGRFULQRORJ\��ƷƵƶƹ�Ʒ�ƾ��ƼƶƾtƷƾ�

DO FLAVONOID-RICH FRUITS AND VEGETABLES ,03529(�9$6&8/$5�)81&7,21"�$QQD�0DFUHDG\

Fruits and vegetables �)9V��KDYH�ORQJ�EHHQ�known to support healthy FDUGLRYDVFXODU��&9��DQG�metabolic function, however public health messages vary between countries with little consensus on type or amount of F&Vs necessary for optimal health. F&Vs contain vitamins, minerals, nitrates and ƮDYRQRLGV��)ODYRQRLGV��IRXQG�LQ�KLJK�TXDQWL-ties in certain F&Vs such as berries, citrus fruits, peppers, onions and broccoli, may improve key markers of CV risk, including YDVFXODU�UHDFWLYLW\��LQƮDPPDWLRQ�DQG�R[LGD-tive stress. However, little is known about the amount and types of F&Vs required for CV health when delivered as whole foods, and there is a need to identify optimal intakes for public health guidance. The FLAvonoids Vascular University of Reading 6WXG\��)/$9856���IXQGHG�E\�WKH�)RRG�Standards Agency was designed to address WKHVH|TXHVWLRQV�

The FLAVURS project, led by Professor Julie Lovegrove was carried out in the University RI�5HDGLQJpV�+XJK�6LQFODLU�8QLW�RI�+XPDQ�1XWULWLRQ��:H�UHFUXLWHG�ƶƼƹ�ORZ�FRQVXPHUV�RI�)9V��DJHG�ƷƻtƼƵ��ZKR�ZHUH�DW�ULVN�IURP�CV disease, from the local Reading area. 'XULQJ�WKLV�ƶƽ�ZHHN�VWXG\��ZH�DVNHG�RXU�SDU-WLFLSDQWV�WR�FRQVXPH�HLWKHU�ƮDYRQRLG�ULFK�RU�ƮDYRQRLG�SRRU�)9V�LQ�LQFUHDVLQJ�GRVHV��two, then four, then six portions per day in addition to their usual diet, over a period of ƶƽ�ZHHNV��:H�DOVR�DVNHG�D�FRQWURO�JURXS�WR�maintain their normal diet and lifestyle and to include no additional F&Vs.

We reported improvements in vascular UHDFWLYLW\�DQG�LQƮDPPDWRU\�PDUNHUV��NH\�indicators of CV risk, for men consuming

D|WRWDO�RI�VL[�SRUWLRQV�RI�KLJK�ƮDYRQRLG�)9V�per day. We also found improvements in SODVPD�QLWULF�R[LGH��12��IRU�ERWK�PHQ�DQG�women consuming a total of seven por-WLRQV�RI�KLJK�ƮDYRQRLG�)9V��12�HQKDQFHV�vascular reactivity and may help to slow the progression of atherogenesis, a key contrib-utor to CV disease. Moreover, participants on the F&Vs diets maintained healthier vascular function and NO levels relative WR|FRQWUROV�GXULQJ�WKH�FRXUVH�RI�WKH�VWXG\��

Results suggest that F&Vs in general provide EHQHƬWV�IRU�KHDOWK\�YDVFXODU�IXQFWLRQ��+LJK�ƮDYRQRLG�)9V�ZHUH�VKRZQ�WR�EH�SDUWLFXODUO\�EHQHƬFLDO��ZLWK�PHQ�LQ�SDUWLFXODU�EHQHƬWLQJ�from eating at least six portions a day.

Macready AL et al. FLAVURS Study Group. Flavonoid-rich fruit and vegetables improve PLFURYDVFXODU�UHDFWLYLW\�DQG�LQƮDPPDWRU\�status in men at risk of cardiovascular GLVHDVH�t�)/$9856��D�UDQGRPL]HG�FRQWUROOHG�trial. $P�-�&OLQ�1XWU��ƷƵƶƹ�0DU�ƾƾ�Ƹ��ƹƼƾtƽƾ�

REDUCING CARDIOVASCULAR DISEASE RISK 7+528*+�5(3/$&(0(17�2)�6$785$7('�)$7�,1b0,/.�$1'�'$,5<�352'8&76�� THE RESET STUDY2RQDJK�0DUNH\

There is an urgent need to focus on modi-ƬDEOH�ULVN�IDFWRUV�IRU�&9'��LQFOXGLQJ�D�KLJK�intake of dietary saturated fatty acids �6)$���:KLOH�UHGXFWLRQ�RI�GDLU\�SURGXFWV�is often recommended for lowering SFA intake, this strategy has been strongly FKDOOHQJHG�EHFDXVH�FRZpV�PLON�LV�D�YLWDO�source of essential micronutrients and proteins, some of which have been associ-DWHG�ZLWK�EHQHƬFLDO�K\SRWHQVLYH�HƪHFWV��Furthermore, prospective evidence sug-gests that high milk consumption is linked to lower risk of CVD. By contrast, altering WKH�IDWW\�DFLG�SURƬOH�RI�PLON�LV�D�SRWHQWLDO�sustainable means of reducing SFA intake at a population level by removing SFA from WKH�IRRG�FKDLQ��ZKLOVW�UHWDLQLQJ�WKH�EHQHƬ-cial aspects of milk.

A BBSRC DRINC funded study led by Professor Givens demonstrated that including processed rapeseeds in the dairy cow diet can reduce SFA content in PLON�IURP�ƼƵ�WR�ƹƺtƻƵ�J�ƶƵƵJ�WRWDO�IDWW\�DFLGV��7)$��ZKLOH�LQFUHDVLQJ�FLV-mono-unsaturated fatty acids (FLV�08)$��IURP�ƷƵ�WR�ƸƸ�J�ƶƵƵJ�7)$��+RZHYHU��WKHUH�LV�D�dearth of research examining the impact

RI�PRGLƬHG�6)$�UHGXFHG�GDLU\�SURGXFWV�on holistic risk markers for CVD, includ-LQJ�YDVFXODU�IXQFWLRQ��SUR�LQƮDPPDWRU\�PHGLDWRUV�DQG|SRVWSUDQGLDO�OLSDHPLD��

In an attempt to reduce this knowledge gap, the MRC-funded RESET (REplace-ment of SaturatEd fat in dairy on Total FKROHVWHURO��6WXG\��OHG�E\�3URI�/RYHJURYH��is investigating the impact of consump-WLRQ�RI�PRGLƬHG�GDLU\�SURGXFWV��WKDW�KDYH�a substantial proportion of SFA replaced with cis-MUFA, on risk factors for CVD. :H�ZLOO�GHWHUPLQH�ZKHWKHU�PRGLƬHG�PLON��cheese and butter intake will improve tra-ditional and novel CVD risk factors, relative to commercially available products. The three-year project, which started in late ƷƵƶƸ��ZLOO�LQIRUP�SXEOLF�KHDOWK�SROLF\�RQ�optimum dietary strategies to prevent or delay the onset of CVD.

:H�DUH�FXUUHQWO\�UHFUXLWLQJ�SDUWLFLSDQWV�IRU�WKH�5(6(7�VWXG\��:H�DUH�ORRNLQJ�IRU�QRQ�VPRNLQJ�PHQ�DQG�ZRPHQ�DJHG�EHWZHHQ�ưƳ�DQG�ƴƳ�\HDUV�WR�WDNH�SDUW��,I�\RX�DUH�LQWHUHVWHG�LQ�ƪQGLQJ�RXW�PRUH�SOHDVH�HPDLO��'U�2RQDJK�0DUNH\��R�PDUNH\#UHDGLQJ�DF�XN

RESEARCH HIGHLIGHTS | ICMR Highlights 9

10

10 ICMR Highlights | IN CONVERSATION

with LUCIA STEFANINI

Dr Lucia Stefanini, formerly Research Assistant Professor in Biochemistry and Biophysics at the University of North Carolina �&KDSHO�+LOO���ZDV�UHFHQWO\�appointed Senior Research Fellow in the School of Biological Sciences as part RI�WKH�8QLYHUVLW\pV�$FDGHPLF�Investment Project. In this recent interview she tells us about her background, research and plans for WKH|IXWXUH�

&RQJUDWXODWLRQV�RQ�\RXU�QHZ�DSSRLQWPHQW��:KDW�DUH�\RXU�UHVHDUFK�LQWHUHVWV"�I am interested in the molecular mecha-nisms by which platelets contribute to health and disease. Platelets are the blood cells that survey the integrity of blood vessels. When we are injured platelets become active and bind to each other to plug the hole and prevent the loss of blood. For our health it is very important that platelet activation is tightly controlled. When platelets numbers are too low or do not activate properly this may cause bleeding, but when platelets are too active they may form aggregates that occlude a vessel and stop the supply of blood and oxygen to important organs such as the heart or the brain. As of today, heart attack and stroke are major causes of mor-bidity and mortality in our society and we KDYHQpW�\HW�IRXQG�D�ZD\�WR�SUHYHQW�WKURPER-sis without causing unwanted bleeding.

:KDW�ZLOO�\RX�EH�LQYHVWLJDWLQJ�KHUH�DW�WKH�8QLYHUVLW\�RI�5HDGLQJ"My research focuses on a class of small G SURWHLQV�FDOOHG�5$3V�WKDW�DUH�WKH�oPROHFXODU�

VZLWFKHVp�RI�SODWHOHW�DFWLYDWLRQ��'XULQJ�P\�postdoctoral training I studied how these SURWHLQV�DUH�oVZLWFKHG�RQp�DW�D�VLWH�RI�LQMXU\��now I am investigating how RAPs, once DFWLYH��oVZLWFK�RQp�WKH�SODWHOHW�LWVHOI��,�WKLQN�WKDW�LI�ZH�XQGHUVWDQG�WKH�oVZLWFKp�ZH�FDQ�OHDUQ�KRZ�WR�FRQWURO�LW�DQG�SRWHQWLDOO\�ƬQH�WXQH�LW�WR�ƬQG�WKH�SHUIHFW�EDODQFH�EHWZHHQ�bleeding and thrombosis.

:KHUH�GLG�\RX�VWXG\�DQG�WUDLQ"I began my studies at the University of Pavia, Italy, where I completed my PhD in Biochem-istry in the laboratory of Prof. Mauro Torti, an H[SHUW�RQ�SODWHOHW�VLJQDOOLQJ��,Q�ƷƵƵƽ�,�PRYHG�to the United States for my postdoctoral training and I joined the laboratory of Prof. :ROIJDQJ�%HUJPHLHU�ƬUVW�DW�7KRPDV�-HI-IHUVRQ�8QLYHUVLW\��3KLODGHOSKLD��DQG�ODWHU�at the University of North Carolina (Chapel +LOO���0\�H[SHULHQFHV�LQ�WKH�WZR�LQVWLWXWLRQV�had a complementary role in my educa-tion. In Philadelphia I had access to various models of cardiovascular disease and I had the opportunity to interact with clinicians DQG�ZRUOG�H[SHUWV�LQ�WKH�SODWHOHW�ƬHOG��ZKLFK�gave me more insight in the role of plate-lets in health and disease. At UNC I worked mainly with biochemists and biophysicists with a strong focus on small G proteins like RAP so I acquired new molecular tools to study these very interesting proteins.

+RZ�GRHV�\RXU�ZRUN�ƪW�LQ�ZLWK�RWKHU�UHVHDUFK�LQ�WKH�,&05�DQG�WKHbUHVHDUFK�SULRULWLHV�RI�WKH�8QLYHUVLW\�DV�D�ZKROH"Cardiovascular and metabolic diseases are the greatest problems of our society and the University has recently decided to invest LQ�WKLV�ƬHOG�DQG�,�ZDV�KHDG�KXQWHG�IRU�WKLV�VSHFLƬF�UHDVRQ��7KH�,&05�XQLWHV�UHVHDUFK�groups that employ very diverse set of WHFKQLTXHV�DQG�VWXG\�GLƪHUHQW�FHOO�PRGHOV�but with a common goal to understand and solve cardiovascular and metabolic dis-eases, thus the potential for collaborations DUH|DVWRXQGLQJ�

:KDW�DUH�WKH�PDLQ�FKDOOHQJHV�\RX�IDFH�UHJDUGLQJ�\RXU�UHVHDUFK"7KH�JUHDWHVW�GLƯFXOW\�LQ�VWXG\LQJ�SODWH-OHWV�LV�WKH�IDFW�WKDW�\RX�FDQpW�PDQLSXODWH�their genetic makeup and we have to rely RQ�PRXVH�PRGHOV�WR�VWXG\�WKH�HƪHFW�RI�D�SURWHLQ�PXWDWLRQ�RU�GHƬFLHQF\��$FFRUGLQJ�to the latest proteomic studies there are DOPRVW�ƺƵƵƵ�SURWHLQV�LQ�SODWHOHWV�DQG�ZH�FDQpW�JHQHUDWH�D�PRXVH�PRGHO�IRU�HDFK��,|WKLQN�WKH�FKDOOHQJH�RI�RXU�JHQHUDWLRQ�ZLOO�EH|WR�ƬQG�QHZ�VWUDWHJLHV�WR�VWXG\�SURWHLQ�functions and dissect signalling pathways LQ|D�PRUH�HƯFLHQW�DQG�OHVV�FRVWO\�PDQQHU�

:KDW�KDYH�EHHQ�\RXU�SURXGHVWbDFKLHYHPHQWV"My proudest achievement is the characteri-]DWLRQ�RI�D�SURWHLQ�FDOOHG�5$6$Ƹ�LQ�SODWHOHWV��)RU�ƸƵ�\HDUV�ZH�KDYH�XVHG�LQKLELWRUV�RI�WKH�SODWHOHW�$'3�UHFHSWRU�3Ʒ<ƶƷ to prevent the formation of occlusive thrombi and about ƶƵ�\HDUV�DJR�LW�ZDV�GHPRQVWUDWHG�WKDW�3Ʒ<ƶƷ FRQWUROV�5$3��WKH�oPROHFXODU�VZLWFKp�,�ZDV�talking about, but nobody knew how. My UHFHQW�ZRUN�GHPRQVWUDWHV�WKDW�5$6$Ƹ�LV�WKH�PLVVLQJ�OLQN�EHWZHHQ�3Ʒ<ƶƷ and RAP and elu-FLGDWHV�IRU�WKH�ƬUVW�WLPH�KRZ�3Ʒ<ƶƷ inhibition DƪHFWV�WKURPEXV�VL]H�DQG�VWDELOLW\�

/RRNLQJ�DKHDG�ZKDW�DUH�\RXU�DLPVbIRU�WKH�QH[W�IHZ�\HDUV"I am in the process of applying for a British Heart Foundation Intermediate Basic Science Fellowship and I am looking forward to establishing my own research group at Reading. In addition I have many ideas for collaborations with ICMR colleagues. I am really excited about a new project in col-laboration with Dr Chris Jones where we will employ the super-resolution microscope that has recently been incorporated in the ICMR imaging facility to study the mecha-QLVPV�UHJXODWLQJ��LQWHJULQ|�FOXVWHULQJ��

In conversation

7RS Archetypical structure of small G proteins

OLNHb5$3V��WKH�PROHFXODU�VZLWFKHV�RI�SODWHOHWV�

11

ICMR TRAVEL AWARD WINNERS | ICMR Highlights 11

&KULV�-RQHV�LV�D�6HQLRU�5HVHDUFK�)HOORZ�who studies genetics and genomics to

JDLQ�LQVLJKW�LQWR�SODWHOHW�VLJQDOOLQJ��&KULV�used this travel award to attend the XXIV

&RQJUHVV�RI�WKH�,QWHUQDWLRQDO�6RFLHW\�RQ�7KURPERVLV�DQG�+DHPDWRVLV�LQ��$PVWHUGDP���1HWKHUODQGV��

0LFKDHO�6FKHQN, a PhD student super�vised by Prof Jon Gibbins, was awarded

an ICMR grant to attend and present at

the XXIV Congress of the International

6RFLHW\�RQ�7KURPERVLV�DQG�+DHPDWRVLV�LQ�$PVWHUGDP��1HWKHUODQGV��7KH�WLWOH�RI�KLV�WDON�ZDV�Ś3ODWHOHWV�SURPRWH�LPPXQRSDWKRORJ\�LQ�3�b%HUJKHL�LQIHFWLRQ�E\�LQKLELWLQJ�WKH�GHYHORSPHQW�RIb,/�ƯƮ�H[SUHVVLQJ�7KƯ�FHOOVś�

&KDUORWWH�0LOOV�is a post graduate

student supervised by Prof Jeremy

6SHQFHU��7KH�WUDYHO�DZDUG�WKDW�VKH�received was used to attend the Inter�national Conference on Polyphenols and

+HDOWK��,&3+��LQ�%XHQRV�$LUHV��$UJHQWLQD��$W�WKH�FRQ�IHUHQFH�VKH�SUHVHQWHG�KHU�ZRUN�RQ�FRƩHH�SRO\SKHQROV�DQG�YDVFXODU�IXQFWLRQbDVbD�SRVWHU��DQG�ZDV�IXUWKHU�DZDUGHG�DQ�,&3+�7UDYHO�3UL]H�DW�WKH�FRQIHUHQFH��

6DUDK�-LQJ�*XR�is a PhD student

supervised by Professors Ian Givens

DQG�-XOLH�/RYHJURYH��6KH�UHFHLYHG�WKH�travel award for attending the Nutrition

6RFLHW\�FRQIHUHQFH�RQ�Ś(JJV�OLIWLQJ�WKH�OLPLWV�DQG�HVWDEOLVKLQJ�WKH�QXWULWLRQDO�EHQHƪWVś��ZKLFK�ZDV�KHOG�DW�WKH�5R\DO�6RFLHW\�RI�0HGLFLQH��/RQGRQ��8.��ƶ�0D\�ưƮƯƱ���

Rekha Rana is a post graduate student

VXSHUYLVHG�E\�3URI�-RQ�*LEELQV��6KH�received the travel award to attend and

present at the XXIV Congress of the

,QWHUQDWLRQDO�6RFLHW\�RQ�7KURPERVLV�DQG�+DHPDWRVLV�LQ�$PVWHUGDP��1HWKHUODQGV��6KH�JDYH�DQ�RUDO�SUHVHQWDWLRQ�RQ�WKH�WRSLF�Ś5ROH�RI�(SK%ư�(SKULQ�VLJQDOOLQJ�LQ��SODWHOHWb�IXQFWLRQś�

)UDQFLV�$WDQX�LV�D�3K'�VWXGHQW�VXSHUYLVHG�E\�3URI�.LP�:DWVRQ��+H�UHFHLYHG�WKH�,&05�&RQIHUHQFH�DQG�7UDYHO�Award to attend and present a poster at the Interna�WLRQDO�&RQIHUHQFH�RQ�%LRLQIRUPDWLFV��&RPSXWDWLRQDO�%LRORJ\�DQG�%LRPHGLFDO�,QIRUPDWLFV�KHOG�LQ�:DVKLQJWRQ�'&��86$���6HSWHPEHUbưư�Ř�ưƳ�ưƮƯƱ���

The other winners were -RUGL�0D\QHULV�3HU[DFKV,

'LDQD�%DUNHU�and $OHMDQGUR�*LUDOGR5DPLUH]�

ICMR TRAVEL AWARD WINNERSAn integral part of ICMR mission is to train young investigators and to promote their attendance to international and national conferences. For this purpose last year the ICMR gave travel awards to nine FDQGLGDWHV�IURP�YDULRXV�ƬHOGV�RI�FDUGLRYDVFXODU�DQG�metabolic research. The following are the list of ICMR travel award winners:

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Advances in biomedical research over the past three decades have led to a ����UHGXFWLRQ�LQ�WKH�GHDWK�UDWH�RI�WKRVH�suffering from cardiovascular disease.

Whilst this is a substantial achievement, the incidence rates for cardiovascular disease are increasing rapidly. It is recognised that conditions such as obesity, and obesity-related metabolic disorders such as type ��GLDEHWHV��DEQRUPDO�OLSLG�PHWDEROLVP��inflammatory disorders and imbalanced diet are at the centre of this increase.

Using a distinctive combination of research approaches and expertise the ICMR is successfully tackling this developing twenty-first-century healthcare crisis from D|QXPEHU�RI�LQQRYDWLYH�GLUHFWLRQV��IRFXVLQJ�on causes, prevention and treatment of these conditions. We aim to reduce the burden of cardiovascular and metabolic disease through our innovative research.

HIGHLIGHTS For more information, please contact:

,QVWLWXWH�IRU�&DUGLRYDVFXODU�5HVHDUFK University of Reading Whiteknights Reading, RG6 6AS

icmr@reading.ac.uk 7HO����������������

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VOLUNTEERS NEEDED FOR STUDIES CONDUCTED $7�7+(b,&05For more information about participating in dietary and other human intervention studies DLPHG�DW�UHGXFLQJ�WKH�ULVN�RI|KHDUW|GLVHDVH��SOHDVH�HPDLO| QXWULWLRQYROXQWHHUV#UHDGLQJ�DF�XN.