Dr Karen GrantDirector of Admissions & Deputy Director of Medical Studies
I have two main areas of research: parasitology and medical education. In parasitology, my research focused on the identification, characterisation and validation of novel drug targets for the medically important protozoan parasites, Leishmania and Trypanosoma brucei, with a particular emphasis on protein kinases. In medical education, my research focuses on evidence-based admissions procedures, the application of learning theories in the medical education context, the use of simulation in medical education and the teaching & assessment of professionalism.
Ongoing research projects include:
- Evaluation of the transferability of skills learnt using simulation into real life practice (in collaboration with Dr Fiona Curtis, Lancaster Medical School, and Dr Jennifer Horrocks, University of Morecambe Bay Foundation Hospital Trust), which aims to contribute to the theory of situated learning, in the context of simulation in medical education; to improve the student learning experience and to maximise the effectiveness of simulated learning used in training medical students. Funded by the Association for the Study of Medical Education.
- Investigation of the impact of introducing the multiple mini interview (MMI) into the selection process for entry to Lancaster Medical School. Areas that are being explored include the long-term predictive validity of the MMI and the impact on the demographics of medical students (gender, age, educational background, socio-economic group).
- The design, delivery and evaluation of a student-led widening participation project (in collaboration with Our Lady’s Catholic College, Lancaster). Areas that are being explored include perceptions of higher education in local school students, progression rates to higher education and specifically progression to medical school (locally and nationally), before and after the initiation of the project.
- How can medical student prescribing skills be improved? Explores factors that can predict poor prescribing performance and evaluates whether different teaching and assessment techniques can improve student drug dose calculation skills.
- What factors influence how medical students choose their Special Study Modules? In collaboration with Dr Kathryn Steven.
My parasitology research focused on the protozoan parasites, Leishmania and Trypanosoma, the infective agents in leishmaniasis and African sleeping sickness respectively. Specifically, I’m interested in the interface between biology and chemistry and the translation of advances in basic biology into the development of novel drugs against these parasitic diseases.
The leishmaniases are a group of diseases, prevalent in the tropics and sub-tropics. They include life-threatening visceral leishmaniasis, cutaneous leishmaniasis, the most common form of the disease, and the seriously disfiguring muco-cutaneous leishmaniasis. The WHO estimate that 12 million people are affected by leishmaniasis in 88, predominantly developing, countries worldwide.
African sleeping sickness affects 36 countries in sub-Saharan Africa. Infection with Trypanosoma parasites results initially in malaise, lethargy and intermittent fever leading to coma and death if the infection spreads to the central nervous system. At present, African sleeping sickness claims relatively few lives but there is a continued threat of a major epidemic, which would a devastating effect on affected areas.
Current first-line chemotherapies for leishmaniasis and African sleeping sickness are far from ideal. They are not particularly effective, have serious toxic side effects and drug resistance is an increasing problem. Thus there is an urgent need for new drugs against these tropical parasitic diseases.
Work within my laboratory aimed to identify and validate novel drug targets, using a combination of molecular biology and classical biochemistry, with a particular interest in protein kinase enzymes and cell cycle control. Previous work validated a leishmanial cyclin-dependent kinase (CDK), CRK3, as a potential drug target and identified CDK inhibitors that had anti-parasitic activity in vitro. In collaboration with synthetic chemists, we attempted to optimise these CRK3 inhibitors using a variety of different approaches, including classical chemical derivatisation and model-based rational drug design.
In medical education, my research interests are wide-ranging but the unifying theme is about improving the quality of the student experience, improving the quality of our graduates and ultimately, improving the patient care delivered by our graduates in the future.
To improve the quality of future doctors, you need to start right at the beginning, before they even begin to study medicine. How can we ensure we select those who will make the best doctors in the future? How can we ensure that we identify those who are not suited to a career in medicine and prevent them entering the profession? One stream of my research revolves around identifying the skills, attributes, attitudes and values that define a ‘good doctor’ and investigating how these can be assessed during the selection process. To ensure that our selection processes are evidence-based and ‘fit for purpose’ requires robust evaluation of their reliability and predictive validity. In light of the recent Milburn report on social mobility, we are also interested in the impact our selection processes have on widening participation and recruitment of medical students from under-represented socio-economic groups.
My medical education research interests continue in the exploration and evaluation of different teaching methods, applying different theories of learning to the various types of learning in which medical students engage. Again, I’m interested in applying the theory to improve the student experience, student learning and, ultimately, their clinical practice. Current areas of interest include the use of simulation in medical education and the teaching and assessment of professionalism.
I contribute to the MBChB degree programme in a number of ways: I am a problem-based learning (PBL) tutor for students in years 1-3, I deliver pharmacology lectures in years 1 and 2, I deliver a number of workshops, in years 1-3, designed to enhance students’ ability to reflect and prescribe safely and I am a special study module (SSM) convenor for students in years 1-3.
Evaluation of the transferability of skills learnt using simulation into real life practice
Horrocks, J.L., Curtis, F., Grant, K. 2014
Proteomic insights into parasite biology
Ginger, M.L., McKean, P.G., Burchmore, R., Grant, K.M. 08/2012 In: Parasitology. 139, 9, p. 1101-1102. 2 p.
High Throughput Screens Yield Small Molecule Inhibitors of Leishmania CRK3:CYC6 Cyclin-Dependent Kinase
Walker, R.G., Thomson, G., Malone, K., Nowicki, M.W., Brown, E., Blake, D.G., Turner, N.J., Walkinshaw, M.D., Grant, K., Mottram, J.C. 5/04/2011 In: PLoS Neglected Tropical Diseases. 5, 4, 11 p.
Recombinant Leishmania mexicana CRK3:CYCA has protein kinase activity in the absence of phosphorylation on the T-loop residue Thr178.
Gomez, F.C., Ali, N.O.M., Brown, E., Walker, R.G., Grant, K.M., Mottram, J.C. 06/2010 In: Molecular and Biochemical Parasitology. 171, 2, p. 89-96. 8 p.
6-Br-5methylindirubin-3′oxime (5-Me-6-BIO) targeting the leishmanial glycogen synthase kinase-3 (GSK-3) short form affects cell-cycle progression and induces apoptosis-like death: Exploitation of GSK-3 for treating leishmaniasis
Xingi, E., Smirlis, D., Myrianthopoulos, V., Prokopios, M., Grant, K., Meijer, L., Mikros, E., Skaltsounis, A., Soteriadou, K. 10/2009 In: International Journal for Parasitology. 39, 12, p. 1289-1303. 15 p.
Malaria ookinetes exhibit multiple markers for apoptosis-like programmed cell death in vitro.
Arambage, S.C., Grant, K.M., Pardo, I., Ranford-Cartwright, L., Hurd, H. 15/07/2009 In: Parasites and Vectors. 2, 1, 16 p.
Trypanosomatid protein kinases as potential drug targets.
Wiese, M., Morris, A., Grant, K.M. 2009 In: Antiparasitic and antibacterial drug discovery : from molecular targets to drug candidates.. Weinheim : Wiley-VCH p. 227-247. 21 p. ISBN: 978-3-527-32327-2.
Targeting the Cell Cycle in the Pursuit of Novel Chemotherapies against Parasitic Protozoa.
Grant, K.M. 2008 In: Current Pharmaceutical Design. 14, 9, p. 917-924. 8 p.
Apoptosis-like death as a feature of malaria infection in mosquitoes.
Hurd, H., Grant, K.M., Arambage, S.C. 03/2006 In: Parasitology. 132, Supple, p. S33-S47.
The selective biological activity of indirubin-based inhibitors : applications in parasitology.
Wells, C., McNae, I., Walkinshaw, M., Westwood, N.J., Grant, K.M. 2006 In: Indirubin, the red shade of indigo. Roscoff, France : Life in Progress Editions p. 259-267. 9 p. ISBN: 2951802900.
Inhibitors of Leishmania mexicana CRK3 Cyclin-Dependent Kinase: Chemical Library Screen and Antileishmanial Activity.
Grant, K.M., Dunion, M.H., Yardley, V., Skaltsounis, A., Marko, D., Eisenbrand, G., Croft, S.L., Meijer, L., Mottram, J.C. 08/2004 In: Antimicrobial Agents and Chemotherapy. 48, 8, p. 3033-3042. 10 p.
Intracellular targets of paullones : identification by affinity chromatography using immobilized inhibitor.
Knockaert, M., Wieking, K., Schmitt, S., Leost, M., Grant, K.M., Mottram, J.C., Kunick, C., Meijer, L. 12/07/2002 In: Journal of Biological Chemistry. 277, 28, p. 25493-25501. 9 p.
The CRK3 protein kinase is essential for cell cycle progression of Leishmania mexicana.
Hassan, P., Fergusson, D., Grant, K.M., Mottram, J.C. 6/04/2001 In: Molecular and Biochemical Parasitology. 113, 2, p. 189-198. 10 p.
Intracellular targets of cyclin-dependent kinase inhibitors: identification by affinity chromatography using immobilised inhibitors.
Knockaert, M., Gray, N., Damiens, E., Chang, Y., Grellier, P., Grant, K.M., Fergusson, D., Mottram, J.C., Soete, M., Dubremetz, J., Le Roch, K., Doerig, C., Schultz, P.G., Meijer, L. 1/06/2000 In: Chemistry and Biology. 7, 6, p. 411-422. 12 p.
Simulation in Medical Education
01/09/2013 → 28/02/2014