Neuroscience & Mental Health Research Institute

Profs. Stephen Dunnett and Anne Rosser

Based at the Brain Repair Group, Neuroscience Group, School of Biosciences

Research Keywords

‘Brain repair’, neural transplantation, stem cells, animal models of Huntington’s and Parkinson’s diseases, motor and cognitive behaviour, preclinical studies for clinical trials

Research Interests

The brain repair group seeks to develop novel cell based therapies to prevent, protect and repair the brain from neurodegeneration, whether caused by damage (trauma, stroke) or disease (Huntington’s, Parkinson’s). The primary focus of the group is on cell transplantation of primary fetal tissues and the development of stem cells as a viable alternative donor source. Our studies develop cell protocols in vitro, explore mechanisms of transplantation, cell survival, growth, connection and function in relevant animal models, and include preclinical studies to generate viable and validated clinical-grade cells in preparation for clinical trials of cell transplantation therapies in human disease. A variety of ancillary programmes support this core developmental stream, including studies on human fetal development; the immunology of cell survival, rejection and immunoprotection in the brain; the development of animal models of human disease; refinement of motor and cognitive assessments sensitive to brain damage and recovery; comparative evaluation of alternative strategies for neuroprotection, regeneration and symptomatic treatment; and the analysis of side effects of drugs and grafts (in particular l-dopa and graft induced dyskinesias).

Laboratory Facilities

The brain repair group operates within a dedicated facility that includes: experimental neurosurgery; automated operant as well as observation and maze based tests of motor and cognitive behaviour; anatomy and immunohistochemistry; research- and clinical-grade cell culture facilities; light, fluorescence and quantitative microscopy; and with direct access to shared confocal and MRI imaging suites. Several projects are undertaken in close collaborations with colleagues expert in imaging ligands (Edwards, Chemistry), molecular genetics of Huntington’s disease (Jones, Psychological Medicine), molecular biology of stem cell development (Allen, Biosciences), electrophysiology of grafted cell integration (Brambilla and Kemp, Biosi) and neuroimmunology (Morgan, Medicine).

Potential areas of PhD Projects

1. Derivation and differentiation of fetal neural, embryonic and germ-line stem cells for neural transplantation;
2. Protocols for preparation of clinical-grade primary and stem cells;
3. Development of better models of disease (including transgenic models), and more sensitive tests of motor and cognitive function for rodents and/or patients;
4. Refining transplantation protocols and theoretical analysis of mechanisms of graft function, in order to maximise functional efficacy of primary and stem cell implants in animal models of relevant human neurodegenerative disease;
5. Quantitative neuroanatomical analysis of human fetal development in order to refine the precision of tissue transplantation sources;
6. Strategies for labelling primary and stem cells in vitro and in vivo, for MRI imaging following transplantation;
7. Neuroimmunology of graft rejection, and development of improved strategies for host immunoprotection or tolerisation.

Sample Publications

1. Dunnett SB, Björklund A (1999) Parkinson's disease: prospects for novel restorative and neuroprotective treatments. Nature suppl 399:32-39.
2. Rosser AE, Dunnett SB (2003) Neural transplantation in patients with Huntington's disease. CNS Drugs 17:853-867.
3. Dunnett SB, Rosser AE (2007) Stem cell transplantation for Huntington's disease. Exp Neurol203:279-292.
4. Torres EM, Monville C, Gates MA, Bagga V, Dunnett SB (2007) Improved survival of young donor age dopamine grafts in a rat model of Parkinson's disease. Neuroscience 146:1606-1617.
5. Kelly CM, Precious SV, Penketh R, Amso NN, Dunnett SB, Rosser AE (2007) Striatal graft projections are influenced by donor cell type and not the immunogenic background. Brain 130:1317-1329.
6. Dowd E, Dunnett SB (2004) Deficits in a lateralised associative learning task in dopamine-depleted rats, with selective recovery by dopamine-rich transplants. Eur J Neurosci 20:1953-1959.
7. Dunnett SB, White A (2006) Striatal grafts alleviate bilateral striatal lesion deficits in operant delayed alternation in the rat. Exp Neurol 199:479-489.
8. Döbrössy MD, Dunnett SB (2001) The influence of environment and experience on neural grafts. Nat Rev Neurosci 2:871-879.
9. Rosser AE, Barker RA, Armstrong RA, Elneil S, Jain M, Hurelbrink CB, Prentice A, Carne C, Thornton SR, Hutchinson H, Dunnett SB (2003) Staging and preparation of human fetal striatal tissue for UK study of neural transplantation in Huntington's disease. Cell Transplant 12:679-686.