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Prof T Heagerty, Dr H Soran
Applications accepted all year round
Self-Funded PhD Students Only
About the Project
The objective of this PhD project is to determine the extent to which low-density lipoprotein (LDL) and atherogenetically modified LDL affect vascular function in vitro. It will also investigate if high-density lipoprotein (HDL) and PON1 restrict the damage induced by LDL.
Foam cells are critical components of atheromatous lesions, the cholesterol droplets in their cytoplasm are derived from LDL. Yet in tissue culture unmodified LDL is taken up only slowly by macrophages. LDL must undergo chemical modification before its uptake is rapid enough for foam cell formation. Naturally-occurring atherogenic modifications of lipoproteins include oxidation and glycation. Recently we have reported that HDL can impede glycation and oxidation of LDL in vitro by mechanisms that involve paraoxonase-1, a protein associated with HDL. Also we have reported that HDL’s antioxidant properties and vascular function improves after bariatric surgery and weight loss. In addition there is recent evidence that components of HDL stimulate beta cell insulin secretion in vitro.
We propose to examine if native LDL and atherogenically modified LDL can cause dysfunction in small arteries in vitro and whether HDL can protect vessels from any dysfunction induced by LDL. Also we propose to investigate if HDL enriched with recombinant PON1 and/or apolipoprotein AI will offer more protection to vessels in vitro.
The successful candidate will gain extensive experience in both cardiovascular science and lipidology as well as basic training in aspects of pharmacology and studies of small arteries. The project is therefore suited to an individual keen to engage in either cardiovascular and/or lipidology research. Upon completion, progression into a postdoctoral career within academia or industry would be anticipated. The study would be conducted within the Cardiovascular Research Group, University of Manchester.
Applicants should hold, or expect to obtain, a minimum upper-second honours degree (or equivalent) in biochemistry, molecular biology or a related area. An appropriate Masters or other post-graduate degrees and previous experience of vitro vascular culture, general laboratory, lipoproteins separation and enrichment techniques would be beneficial but are not essential.
This 3-year project is open to UK/EU and non-EU nationals but no funding is provided. Applicants must therefore be able to evidence their ability to provide self-arranged funding. Annual tuition fees for this project are currently:
*UK/EU nationals: £17, 600
Non-EU nationals: £28, 300
Please direct applications in the following format to Professor Tony Heagerty ([Email Address Removed]) and Dr Handrean Soran ([Email Address Removed]).
• Academic CV
• Official academic transcripts
• Contact details for two suitable referees
• A personal statement (750 words maximum) outlining your suitability for the study, what you hope to achieve from the PhD and your research experience to date.
• Evidence of funding.
Any enquiries relating to the project and/or suitability should be directed to Professor Anthony Heagerty or Dr Handrean Soran.
Foam cells are critical components of atheromatous lesions, the cholesterol droplets in their cytoplasm are derived from LDL. Yet in tissue culture unmodified LDL is taken up only slowly by macrophages. LDL must undergo chemical modification before its uptake is rapid enough for foam cell formation. Naturally-occurring atherogenic modifications of lipoproteins include oxidation and glycation. Recently we have reported that HDL can impede glycation and oxidation of LDL in vitro by mechanisms that involve paraoxonase-1, a protein associated with HDL. Also we have reported that HDL’s antioxidant properties and vascular function improves after bariatric surgery and weight loss. In addition there is recent evidence that components of HDL stimulate beta cell insulin secretion in vitro.
We propose to examine if native LDL and atherogenically modified LDL can cause dysfunction in small arteries in vitro and whether HDL can protect vessels from any dysfunction induced by LDL. Also we propose to investigate if HDL enriched with recombinant PON1 and/or apolipoprotein AI will offer more protection to vessels in vitro.
The successful candidate will gain extensive experience in both cardiovascular science and lipidology as well as basic training in aspects of pharmacology and studies of small arteries. The project is therefore suited to an individual keen to engage in either cardiovascular and/or lipidology research. Upon completion, progression into a postdoctoral career within academia or industry would be anticipated. The study would be conducted within the Cardiovascular Research Group, University of Manchester.
Applicants should hold, or expect to obtain, a minimum upper-second honours degree (or equivalent) in biochemistry, molecular biology or a related area. An appropriate Masters or other post-graduate degrees and previous experience of vitro vascular culture, general laboratory, lipoproteins separation and enrichment techniques would be beneficial but are not essential.
This 3-year project is open to UK/EU and non-EU nationals but no funding is provided. Applicants must therefore be able to evidence their ability to provide self-arranged funding. Annual tuition fees for this project are currently:
*UK/EU nationals: £17, 600
Non-EU nationals: £28, 300
Please direct applications in the following format to Professor Tony Heagerty ([Email Address Removed]) and Dr Handrean Soran ([Email Address Removed]).
• Academic CV
• Official academic transcripts
• Contact details for two suitable referees
• A personal statement (750 words maximum) outlining your suitability for the study, what you hope to achieve from the PhD and your research experience to date.
• Evidence of funding.
Any enquiries relating to the project and/or suitability should be directed to Professor Anthony Heagerty or Dr Handrean Soran.
Funding Notes
*UK/EU nationals should note that the tuition fee is subject to an annual increase of approximately 2.5%
References
1. Younis NN, Soran H, Pemberton P, Charlton-Menys V, Durrington P. Small dense LDL in Type 2 Diabetes is Preferentially Glycated. Diabetes and Vascular Disease Research 2010; 7: 289-295.
2. Younis NN, Charlton-Menys V, Sharma R, Soran H, Durrington PN. Glycation of LDL in non-diabetic people: small dense LDL is preferentially glycated both in vivo and in vitro. Atherosclerosis 2009; 202: 162-168.
3. Soran H, Charlton-Menys V, Younis NN, Durrington PN. Variation in Paraoxonase-1 and atherosclerosis Current Opinion in Lipidology 2009; 20: 265-74.
4. Greenstein AS, Khavandi K, Withers SB, Sonoyama K, Clancy O, Jeziorska M, Laing I, Yates AP, Pemberton PW, Malik RA, Heagerty AM. Local inflammation and hypoxia abolish the protective anticontractile properties of perivascular fat in obese patients. Circulation. 2009; 119: 1661-70.
5. Younis NN, Sharma R, Soran H, Charlton-Menys V, Elseweidy M, Durrington PN. Glycation as an atherogenic modification of LDL. Curr Opin Lipidol. 2008; 19: 378-84.
6. Greenstein AS, Paranthaman R, Burns A, Jackson A, Malik RA, Baldwin RC, Heagerty AM. Cerebrovascular damage in late-life depression is associated with structural and functional abnormalities of subcutaneous small arteries. Hypertension. 2010 Oct; 56: 734-40.
2. Younis NN, Charlton-Menys V, Sharma R, Soran H, Durrington PN. Glycation of LDL in non-diabetic people: small dense LDL is preferentially glycated both in vivo and in vitro. Atherosclerosis 2009; 202: 162-168.
3. Soran H, Charlton-Menys V, Younis NN, Durrington PN. Variation in Paraoxonase-1 and atherosclerosis Current Opinion in Lipidology 2009; 20: 265-74.
4. Greenstein AS, Khavandi K, Withers SB, Sonoyama K, Clancy O, Jeziorska M, Laing I, Yates AP, Pemberton PW, Malik RA, Heagerty AM. Local inflammation and hypoxia abolish the protective anticontractile properties of perivascular fat in obese patients. Circulation. 2009; 119: 1661-70.
5. Younis NN, Sharma R, Soran H, Charlton-Menys V, Elseweidy M, Durrington PN. Glycation as an atherogenic modification of LDL. Curr Opin Lipidol. 2008; 19: 378-84.
6. Greenstein AS, Paranthaman R, Burns A, Jackson A, Malik RA, Baldwin RC, Heagerty AM. Cerebrovascular damage in late-life depression is associated with structural and functional abnormalities of subcutaneous small arteries. Hypertension. 2010 Oct; 56: 734-40.
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