Project Summary
The Mitolab is interested in how cellular energy shapes and is shaped by things like getting older, diseases, exercise and the environment. We also look to see how drugs used to treat disease might affect cell metabolism. Researchers in the lab look at mitochondrial biology since mitochondria are the cell components which produce a large amount of the energy required. We look at human muscle, nerve cells, liver cells, fish muscle and brain, bumble bees, fruit flies and cow liver and milk. The skills that the summer student would learn could be applied to any of the projects we work on. One particularly interesting study focusses upon the treatment for psychosis. The student would learn how to grow nerve cells, treat them with different drugs and then measure the metabolism of the cells using a technique called high resolution respirometry. All the work would be done with guidance and support from other members of the group which includes BBSRC DTP students. Opportunities to meet collaborators, clinical colleagues and other research groups, to attend talks, seminars and lab meetings will also be part of the experience.
Full Project Description
Antipsychotic medications are the mainstay of treatment of psychosis. One of the majorside-effects of these medications is metabolic impairment, which increases the risk ofcardiometabolic diseases. Patients with psychosis are twice as likely, compared to generalpopulations, to die of cardiometabolic diseases. Antipsychotics differ in their propensity tocause metabolic derangements: clozapine and olanzapine (high risk), risperidone andquetiapine (moderate risk), and haloperidol and lurasidone (low risk). Patients also differ intheir susceptibility to develop metabolic side-effects with different antipsychotics. It is onlyafter patients are on antipsychotic treatment, often for weeks and months, before theseside-effects become problematic and strategies, like lifestyle changes and medications likemetformin, to mitigate these are instituted. Besides increasing the risk of cardiometabolicdiseases, these side-effects also affect the therapeutic relationship adversely, contribute topoor treatment concordance and increase the risk of relapse. There is a critical need for a abetter understanding of the cellular response to these medications which will lead tostrategies to inform treatment options, which minimise cardiometabolic risks and reduceassociated morbidity and mortality.Mitochondrial dysfunction is a crucial process that can explain antipsychotic inducedmetabolic derangements. Mitochondrial metabolism can be accurately profiled using high resolutionrespirometry (HRR) techniques. The student will use HRR to accurately define themetabolic signatures that different antipsychotics elicit in cell lines, primary cells and humantreated and untreated (control) blood cells, to stratify the risk of developing metabolicsyndrome and identify which among the treatment options, like metformin, mitigate orreverse those changes.Primarily the student will learn to grow human neuronal cell lines and primary neuronal cells. Once proficient at cell culture (2 weeks), the student will learn to use the Oroboros O2K high resolution respirometer, an instrument used to measure respiration of the cells including oxygen consumption, ATP production, ROS analysis and other relevant measurements. Several protocols will be mastered using the cells the student has grown. Once proficient the student will treat the cells with drug combinations to reveal their effect on mitochondrial function and bioenergetics of the cells.