Fully funded 4 Year PhD studentships available
in the Department of Molecular Biology and Biotechnology
commencing 1 October 2013
Early applications are advisable
The Department offers full time PhD research projects which are fully funded for 4 years. The funding will pay the UK/ EU tuition fees and a maintenance stipend at the RCUK standard rate (£13,590 in 2013/14).
How to apply:
Complete an online application (http://www.shef.ac.uk/postgraduate/research/apply) form for admission as a postgraduate student.
Eligibility
Applicants should have, or expect to achieve, a minimum of an upper-second-class Honours degree (2.1 or above) in a relevant subject.
Project supervisor:
Dr Sherif El-Khamisy (Kerbs Institute / Department of Molecular Biology and Biotechnology)
Project title: The Repair of oxidative and topoisomerase induced chromosomal breaks and human neurodegenerative disease
A fully funded 4-year PhD studentship is available in the laboratory of Dr Sherif El-Khamisy to characterize the mechanisms of repairing oxidative and topoisomerase-mediated DNA damage and their impact on neuronal integrity. Oxidative stress and abortive activities of DNA topoisomerases are among the most common causes of DNA lesions in eukaryotic cells. Defective repair of this class of DNA breakage has been associated with hereditary neurodegenerative disease (El-Khamisy et al., Nature, 434: 108-113, 2005). Cells employ different mechanisms to rapidly and efficiently repair these breaks, including the hydrolytic cleavage of the covalent linkage between the stalled topoisomerase and DNA. The prototype enzyme for this activity is TDP1, which is also involved in the repair of a variety of oxidative DNA termini (El-Khamisy, EMBO Mol Med, 3(2): 78-88, 2011). Mutation in TDP1 causes accumulation of DNA single-strand breaks and human ataxia and its activity is tightly regulated by posttranslational protein modifications such as phosphorylation and SUMOylation (Hudson et al., Nature Commun, 0.1038/mcomms1739, 2012). Despite this important catalytic function fulfilled by TDP1, it remains together with the recently identified enzyme TDP2 (Ledesma et al., Nature, 461:674-8, 2009) the only known human enzymes that display this activity in mammalian cells. Successful candidates will characterise and identify the mechanisms by which human cells repair this type of DNA damage and the consequences of their defect with respect to genetic integrity of post-mitotic tissue. Candidates will receive training on molecular biology techniques, cellular and biochemical DNA repair assays, advanced imaging, and mammalian cell culture. You will work closely with the medical school and with the state-of-the-art Sheffield Institute of Translational Neuroscience.
Candidates should have, or expect to achieve, a minimum of an upper-second-class Honors degree (2.1 or above) in biochemistry, cell biology, or a related subject. Candidates are expected to be enthusiastic, highly committed, and able to deliver high quality research outputs.
Biological research at Sheffield has been ranked 5th in the UK (The Sunday Times Good University Guide 2012) and 37th in the world (Times Higher Education World University Rankings 2012). You will be based at the department of molecular biology and biotechnology in Firth court where Hans Krebs conducted his Nobel Prize winning experiments that led to the discovery of the tricarboxylic acid cycle. A hallmark of the Department is its collaborative ethos where more than half of the research output resulting from fruitful national and international collaborations.
Informal enquiries should be addressed to Dr Sherif El-Khamisy by Email: S.El-Khamisy@sheffield.ac.uk
Project supervisor:
Dr Sherif El-Khamisy
Project title: The Repair of chromosomal single-strand breaks: mechanisms and implications for cancer formation and therapy
A fully funded 4-year PhD studentship is available in the laboratory of Dr Sherif El-Khamisy to examine the mechanisms of repairing the most common forms of endogenous DNA breakage in mammalian cells; those that occur in one strand of DNA (single-strand breaks; SSBs). In addition to their potential contribution to tumor cell formation, accumulation of SSBs underlies the clinical utility of a variety of anti-cancer therapies such as topoisomerase poisons and ionizing radiation. In addition, defects in their repair have been associated with human ataxia (El-Khamisy et al., Nature, 434: 108-113, 2005) and has been widely exploited in synthetic lethal approaches to improve anti-cancer strategies (Bryant et al., Nature 2005). Cells employ different mechanisms to rapidly and efficiently repair these breaks, including the hydrolytic cleavage of the covalent linkage between the stalled topoisomerase and DNA. The prototype enzyme for this activity is TDP1, which is also involved in the repair of a variety of oxidative DNA termini (El-Khamisy, EMBO Mol Med, 3(2): 78-88, 2011). TDP1 function is tightly regulated by posttranslational protein modifications such as phosphorylation and SUMOylation (Hudson et al., Nature Commun, 0.1038/mcomms1739, 2012). Despite this important catalytic function fulfilled by TDP1, it remains together with the recently identified enzyme TDP2 (Ledesma et al., Nature, 461:674-8, 2009) the only known human enzymes that display this activity in mammalian cells. Successful candidates will characterise and identify the mechanisms by which human cells repair this type of DNA damage and utilize this knowledge to improve cancer therapy. Candidates will receive training on molecular biology and proteomic techniques, cellular and biochemical DNA repair assays, advanced imaging, siRNA, and mammalian cell culture. You will work closely with the Sheffield Cancer Research UK Center at the medical school and engage in collaborative environment across the chemical, biological and clinical sciences to translate fundamental research discoveries within the University into potential new medicines.
Candidates should have, or expect to achieve, a minimum of an upper-second-class Honors degree (2.1 or above) in biochemistry, cell biology, or a related subject. Candidates are expected to be enthusiastic, highly committed, and able to deliver high quality research outputs.
Biological research at Sheffield has been ranked 5th in the UK (The Sunday Times Good University Guide 2012) and 37th in the world (Times Higher Education World University Rankings 2012). You will be based at the department of molecular biology and biotechnology in Firth court where Hans Krebs conducted his Nobel Prize winning experiments that led to the discovery of the tricarboxylic acid cycle. A hallmark of the Department is its collaborative ethos where more than half of the research output resulting from fruitful national and international collaborations.
Informal enquiries should be addressed to Dr Sherif El-Khamisy by Email: S.El-Khamisy@sheffield.ac.uk
Project Supervisor:
Dr Karim Sorefan
Project Title: The Role of microRNAs in Development
MicroRNAs (miRNAs) are a highly conserved class of small non-coding RNAs that play an important role in regulating the expression of messenger RNAs. These gene regulators have critical roles in regulating plant development1. Our recent data suggests that multiple miRNA pathways regulate plant growth and these pathways are coordinated by an upstream transcription factor. The successful candidate will use molecular-genetic approaches together with novel next generation sequencing analysis2 to decipher the molecular mechanisms regulating plant growth and development. There will also be an opportunity to have training in bioinformatic analysis of next generation sequencing data and apply the research to improve crop yields should the candidate express an interest.
References:
| Rubio-Somoza I, Weigel D (2011) MicroRNA networks and developmental plasticity in plants. Trends Plant Sci 16: 258-264 | |
| Sorefan K, Pais H, Hall AE, Kozomara A, Griffiths-Jones S, Moulton V, Dalmay T (2012) Reducing sequencing bias of small RNAs. Silence 3: 4 |
For further information contact: Dr Karim Sorefan (k.sorefan@sheffield.ac.uk)