I am a Research Associate and my role in the team is to investigate some of the safety issues surrounding the novel IVF-based techniques being developed to prevent transmission of mitochondrial DNA disease. My research involves performing genetic analysis on eggs that have undergone mitochondrial replacement to determine the safety and efficacy of the procedure. The project requires a close working relationship with the clinical/embryology staff at the Newcastle Fertility Centre and other members of the research team. I feel very privileged that I have been given the opportunity to work on such a pioneering project and I am constantly motivated by the thought that we may be able to help women with mitochondrial DNA disease have healthy children.
Preventing the transmission of mitochondrial DNA disease
Other staff members involved: Laura Irving, Dimitrious Kalleas, Jessica Richardson, Louise Heslop, Staff at the Newcastle Fertility Centre
Mitochondrial DNA is strictly maternally inherited and so a woman with mitochondrial disease due to a mitochondrial DNA mutation is at significant risk of passing the defect to her children. We have demonstrated that it is possible to prevent this transmission using a technique known as pronuclear transfer between human zygotes (Craven et al, 2010). This technique involves removing the pronuclei (which contain the nuclear DNA) from a zygote containing mutant mitochondria and transferring them to an enucleated donor zygote that contains healthy mitochondria.
Initial studies were performed using abnormally fertilised human zygotes to optimise the pronuclear transfer technique. The work currently ongoing involves optimising the procedure between normally fertilised human zygotes donated to research. Work is also underway to determine the efficacy and safety of pronuclear transfer in human zygotes with the ultimate aim of translating this research into clinical treatment.
Sponsor/Funder: Wellcome Trust
Wellcome Trust: http://www.wellcome.ac.uk/About-us/Policy/Spotlight-issues/Mitochondrial-diseases/index.htm
Department of Health: https://www.gov.uk/government/consultations/serious-mitochondrial-disease-new-techniques-to-prevent-transmission
Nuffield Council on Bioethics: http://nuffieldbioethics.org/project/mitochondrial-dna-disorders/
Muscular Dystrophy Campaign: http://www.muscular-dystrophy.org/research/news/7367_mitochondrial_ivf_q_a
Chinnery PF, Craven L, Mitalipov S, Stewart JB, Herbert M, Turnbull DM, The challenges of mitochondrial replacement. PLoS Genet. 2014 Apr 24;10(4):e1004315. doi: 10.1371/journal.pgen.1004315.
Greggains GD, Lister LM, Tuppen HA, Zhang Q, Needham LH, Prathalingam N, Hyslop LA, Craven L, Polanski Z, Murdoch AP, Turnbull DM, Herbert M, Therapeutic potential of somatic cell nuclear transfer for degenerative disease caused by mitochondrial DNA mutations. Sci Rep. 2014 Jan 24;4:3844. doi: 10.1038/srep03844.
Craven L, Elson J, Irving L, Tuppen HA, Lister LM, Greggains GD, Byerley S, Murdoch AP, Herbert M, Turnbull D. Mitochondrial DNA disease: new options for prevention. Hum Mol Genet. 2011 Oct 15;20(R2):R168-74. doi: 10.1093/hmg/ddr373.
Craven L, Tuppen HA, Greggains GD, Harbottle SJ, Murphy JL, Cree LM, Murdoch AP, Chinnery PF, Taylor RW, Lightowlers RN, Herbert M, Turnbull DM. Pronuclear transfer in human embryos to prevent transmission of mitochondrial DNA disease. Nature. 2010;465(7294):82-5. doi: 10.1038/nature08958.
Gardner JL, Craven L, Turnbull DM, Taylor RW. Experimental strategies towards treating mitochondrial DNA disorders. Biosci Rep. 2007 Jun;27(1-3):139-50.
Brown DT, Herbert M, Lamb VK, Chinnery PF, Taylor RW, Lightowlers RN, Craven L, Cree L, Gardner JL, Turnbull DM. Transmission of mitochondrial DNA disorders: possibilities for the future. Lancet. 2006 Jul 1;368(9529):87-9.
PhD thesis submitted January 2010: Mitochondrial Studies in Oocytes and Early Embryos.
Presented at a ‘Mitochondrial Matters’ public engagement event, July 2014, Newcastle upon Tyne.
Selected speaker at the Preimplantation Genetic Diagnosis International Society (PGDIS) Annual Meeting, April 2014, Canterbury.
Selected speaker at the Wellcome Trust Scientific Conference “Mitochondrial Disease: Translating biology into new treatments”, October 2013 Cambridge.
Scientific expert at a HFEA Public Dialogue Event to discuss mitochondrial replacement techniques, July 2012, Cardiff.
Speaker at a fundraising event organised to raise money for mitochondrial research, September 2014, Liverpool.
Attended a drop-in session on mitochondrial donation hosted by Julian Huppert MP on behalf of the Lily Foundation at the Houses of Parliament, September 2014, London.
Speaker in a focus group at the 4th Annual Patient Information Day, April 2012, Newcastle upon Tyne.
Poster presentation at the Muscular Dystrophy Campaign (MDC) National Conference, October 2011, Nottingham.
Speaker at a Mitochondrial Research Group (MRG) Patient Focus Group to discuss the current reproductive options for patients with mitochondrial disease, March 2011, Newcastle upon Tyne.