Tom Kindlon's post to co-cure Jan 1 10
Dept/School Faculty of Medical Sciences Graduate School, Newcastle University
Project Supervisor(s) Dr P Manning
Funding Availability Directly Funded Project (European/UK Students Only)
Application Deadline Applications accepted all year round
Development of Intracellular Nanosensors to Investigate Muscle Bioenergetic Abnormalities Potentially Associated with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS)
Myalgic Encephalomyelitis (ME)/Chronic Fatigue Syndrome (CFS) is characterised by profound fatigue which frequently has a significant impact on quality of life. Research within our group has demonstrated that a significant subgroup of ME/CFS patients exhibit impaired energy generation in muscle.
Pyruvate dehydrogenase complex (PDC) plays a key role in the regulation of cellular energetics. Decreased function of PDC results in increased metabolism of pyruvate via the lactate dehydrogenase pathway, with subsequent overproduction of lactic acid. Impaired energy generation by muscle, an increase in the lactate/pyruvate ratio in ME/CFS, and a propensity towards excess intra-muscular acidosis following limited exercise suggests PDC dysfunction in muscles of ME/CFS patients, with implications for the mechanism of expression of fatigue.
We postulate that patients with ME/CFS have significant abnormality in acid control within their muscles related to both acid eneration and its clearance from tissue which, we believe, results in generation of a centrally-perceived exercise stop signal.
This integrated MRes/PhD studentship will develop intracellular nanosensors specifically designed to monitor real-time fluxes in key analytes within the cell that are associated with critical bioenergetic pathways. In this way it will be possible to identify, with exquisite sensitivity, biochemical changes that ultimately lead to the ME/CSF phenotype. Such sensors will include, but not be limited to, key analytes such as pyruvate, lactic acid, pH and ATP. Further, surface modification of the nanosensor will facilitate the site selective positioning of nanosensors within the cell, thus enabling organelle-directed measurements of metabolite flux in
real time.
The multidisciplinary nature of the supervisory team, which ranges from chemists to clinicians, represents an exceptional combination of skill sets which will enable the delivery of an outstanding research training opportunity to the successful candidate.
Project start date: September 2010
Funding Notes Sponsor: MRC
Eligibility and Value of the Award
Depending on how you meet the MRCs eligibility criteria, you may be entitled to a full or a partial award. A full award covers tuition fees and an annual stipend of 13,290 (2009/10). A partial award covers fees only.
Person Specification
You should have, or expect to achieve, a first-class or upper-second-class Honours degree in a subject related to biomedical sciences.
How to Apply
The University's postgraduate application form must be completed; selecting Master of Research/Doctor of Philosophy - Medical Sciences (Cellular Medicine)as the programme of study and inserting the reference number ICM85. Only mandatory fields need to be completed (no personal statement required) and a CV, a covering letter must be attached. The covering letter must state the title of the studentship, quote the reference number ICM85 and state how your interests and experience relate to the project
[B]PhD studentship: "Development of Intracellular Nanosensors to Investigate Muscle Bioenergetic Abnormalities Potentially Associated with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS)"[/B]
Dept/School Faculty of Medical Sciences Graduate School, Newcastle University
Project Supervisor(s) Dr P Manning
Funding Availability Directly Funded Project (European/UK Students Only)
Application Deadline Applications accepted all year round
Development of Intracellular Nanosensors to Investigate Muscle Bioenergetic Abnormalities Potentially Associated with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS)
Myalgic Encephalomyelitis (ME)/Chronic Fatigue Syndrome (CFS) is characterised by profound fatigue which frequently has a significant impact on quality of life. Research within our group has demonstrated that a significant subgroup of ME/CFS patients exhibit impaired energy generation in muscle.
Pyruvate dehydrogenase complex (PDC) plays a key role in the regulation of cellular energetics. Decreased function of PDC results in increased metabolism of pyruvate via the lactate dehydrogenase pathway, with subsequent overproduction of lactic acid. Impaired energy generation by muscle, an increase in the lactate/pyruvate ratio in ME/CFS, and a propensity towards excess intra-muscular acidosis following limited exercise suggests PDC dysfunction in muscles of ME/CFS patients, with implications for the mechanism of expression of fatigue.
We postulate that patients with ME/CFS have significant abnormality in acid control within their muscles related to both acid eneration and its clearance from tissue which, we believe, results in generation of a centrally-perceived exercise stop signal.
This integrated MRes/PhD studentship will develop intracellular nanosensors specifically designed to monitor real-time fluxes in key analytes within the cell that are associated with critical bioenergetic pathways. In this way it will be possible to identify, with exquisite sensitivity, biochemical changes that ultimately lead to the ME/CSF phenotype. Such sensors will include, but not be limited to, key analytes such as pyruvate, lactic acid, pH and ATP. Further, surface modification of the nanosensor will facilitate the site selective positioning of nanosensors within the cell, thus enabling organelle-directed measurements of metabolite flux in
real time.
The multidisciplinary nature of the supervisory team, which ranges from chemists to clinicians, represents an exceptional combination of skill sets which will enable the delivery of an outstanding research training opportunity to the successful candidate.
Project start date: September 2010
Funding Notes Sponsor: MRC
Eligibility and Value of the Award
Depending on how you meet the MRCs eligibility criteria, you may be entitled to a full or a partial award. A full award covers tuition fees and an annual stipend of 13,290 (2009/10). A partial award covers fees only.
Person Specification
You should have, or expect to achieve, a first-class or upper-second-class Honours degree in a subject related to biomedical sciences.
How to Apply
The University's postgraduate application form must be completed; selecting Master of Research/Doctor of Philosophy - Medical Sciences (Cellular Medicine)as the programme of study and inserting the reference number ICM85. Only mandatory fields need to be completed (no personal statement required) and a CV, a covering letter must be attached. The covering letter must state the title of the studentship, quote the reference number ICM85 and state how your interests and experience relate to the project