Disorders of Sex Development

Lead Research Organisation: MRC Mammalian Genetics Unit

Abstract

The gonads - the testis and ovary - form in the embryo during a process known as organogenesis, a very complex event controlled by a series of changes in which genes are expressed by cells, and their daughters, during development. Disorders in this process cause diseases that are debilitating and costly to our society. This project aims to identify genes functioning during gonad development and offer a way of understanding mechanisms underpinning heritable birth defects at the level of individual molecules. At a more basic level, this programme aims to understand how signaling molecules – proteins which can interpret information and carry it from one part of a cell to another – can regulate the expression of genes in the nucleus of a cell.
In order to isolate and study the function of such genes we need to observe the consequences of inactivating them or altering them in a defined manner. Because a complex organ such as a gonad is built by many different types of cell interacting during development, only the whole animal model is appropriate for such studies. The mouse is an excellent model organism to study sexual development because its reproductive organs are very similar to those of humans.

Technical Summary

My programme is investigating the mechanisms by which signaling events impact on gene expression using cell fate determination in the embryonic mouse gonad as a model system. The “decision” as to whether an embryo develops as a male or a female is known as sex determination and in mammals this process requires expression of the Y-linked gene SRY in XY embryos to establish commitment of the gonadal primordium, in particular somatic cells, to a testicular fate. In recent years we have established a role for mitogen-activated protein kinase (MAPK) signaling in testis determination. Using a forward genetic screen in mice we identified the boygirl mutant, which causes XY gonadal sex reversal due to loss of the kinase MAP3K4. Analysis of XY gonad development in mutant embryos revealed a reduction in Sry expression at a key stage, leading to ovary development. Our studies in mice became directly disease-relevant when we collaborated with clinical geneticists and identified mutations in MAP3K1 as the cause of XY sex reversal in humans. This suggests that MAPK signaling plays an important role in mouse and human testis determination and disruption to the signal transduction pathway may underlie additional disorders of sex development (DSD) in humans. MAP3K1 is now a gene routinely screened during diagnosis of novel cases of DSD. More recently we have been focusing on how an essentially ubiquitous signaling pathway such as MAPK is employed in a time- and tissue-dependent fashion so as to cause specific phenotypes when disrupted. We demonstrated that mice lacking GADD45g also exhibit XY gonadal sex reversal, again due to a disruption to Sry expression. Analysis of MAPK signaling in gonads from Gadd45g and Map3k4 mutants revealed a reduction in the activation of p38 MAPK. We also examined the phosphorylation status of GATA4, a protein known to regulate Sry expression, and showed that in Gadd45g and Map3k4 mutants, pGATA4 levels were significantly reduced. Thus, a GADD45g/MAP3K4/p38 MAPK/GATA4 pathway is implicated in the control of Sry expression during testis determination. The study of the regulation of gene expression requires an understanding of how chromatin modifications are controlled: in this programme our focus is on how signals to the epigenome regulate the expression of testis determining genes. It is notable that in other contexts all the molecules we have established as testis-determining have been shown to directly or indirectly affect chromatin. Examining chromatin structure and occupancy in vivo is challenging in a system where tissue availability is limiting. However, technological progress in the area of epigenomics is rapid and it is becoming feasible to examine genome-wide studies of chromatin using just a few thousand cells. Utilising reporter lines that will allow purification of gonadal somatic cells, and our unique collection of mutants disrupting testis determination, it is our aim to examine the transcriptomics and associated chromatin modifications that underlie normal testis development and those disrupted in the mutants we have characterized. The ultimate aim is to determine the epigenomics of testis determination in vivo and establish how signaling molecules, in particular, regulate this process. We are also collaborating with clinical geneticists attempting to identify novel genes causing DSDs in humans using exome and whole genome sequencing. We are generating and studying sexual development in mice with mutations in candidate genes identified in this way: this will aid in confirming pathogenicity and provides mechanistic insight into genetic pathways underlying DSDs in the human population.

Publications

10 25 50
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Andy Greenfield (2013) Textbook of Clinical Embryology

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Carré GA (2014) Characterising novel pathways in testis determination using mouse genetics. in Sexual development : genetics, molecular biology, evolution, endocrinology, embryology, and pathology of sex determination and differentiation

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Field S (2011) Pkd1l1 establishes left-right asymmetry and physically interacts with Pkd2. in Development (Cambridge, England)

 
Description Briefed the Minister for Public Health and advisors on mitochondrial replacement technologies at Department of Health
Geographic Reach National 
Policy Influence Type Implementation circular/rapid advice/letter to e.g. Ministry of Health
 
Description Chair of 2016 expert panel on safety and efficacy of mitochondrial donation techniques
Geographic Reach Multiple continents/international 
Policy Influence Type Participation in a advisory committee
Impact In 2016 the HFEA convened its 4th expert panel to produce a report on the science of mitochondrial donation techniques. I chaired the expert panel (as I did the one in 2014). The purpose of this report was to advise the HFEA on whether these techniques are suitable for introduction into clinical practice. On the basis of this report the HFEA decided to permit clinics to apply for a license to perform mitochondrial donation. The first license application will be considered in Spring 2017, suggesting that clinical use will follow shortly thereafter. The report and the HFEA decision gave rise to media coverage in the UK and internationally. See: http://www.hfea.gov.uk/10563.html and http://www.hfea.gov.uk/10559.html http://www.bbc.co.uk/news/health-38328097
URL http://www.hfea.gov.uk/10559.html
 
Description Chair of Expert Panel that assessed the safety and efficacy of MST and PNT as methods for mitochondrial replacement
Geographic Reach National 
Policy Influence Type Participation in a advisory committee
URL http://www.hfea.gov.uk/8807.html
 
Description Chair of Genome Editing Working Group for Nuffield Council on Bioethics
Geographic Reach Multiple continents/international 
Policy Influence Type Participation in a national consultation
Impact The report of this working group was published in 2016: http://nuffieldbioethics.org/project/genome-editing/ethical-review-published-september-2016/ There was considerable coverage of the report in the national and even international media e.g. http://www.bmj.com/content/354/bmj.i5318, http://www.nature.com/news/uk-bioethicists-eye-designer-babies-and-crispr-cows-1.20713 and http://www.bbc.co.uk/news/health-37509170 https://www.theguardian.com/science/2016/sep/30/experts-warn-home-gene-editing-kits-pose-risk-to-society The report forms part of an ongoing engagement with issues concerning the safety and efficacy of genetic technologies and their ethical/social implications.
URL http://nuffieldbioethics.org/project/genome-editing/
 
Description Chair of expert panel assessing the safety and efficacy of polar body transfer as a means of preventing inheritance of mitochondrial diseases
Geographic Reach National 
Policy Influence Type Participation in a advisory committee
URL http://www.hfea.gov.uk/8807.html
 
Description Evidence given to House of Commons Science and Technology Select Committee on human genome editing
Geographic Reach National 
Policy Influence Type Gave evidence to a government review
URL http://data.parliament.uk/writtenevidence/committeeevidence.svc/evidencedocument/science-and-technol...
 
Description Invited speaker at 2nd International Summit on Human Genome editing
Geographic Reach Multiple continents/international 
Policy Influence Type Participation in a national consultation
URL http://www.nationalacademies.org/gene-editing/2nd_summit/
 
Description Member of ISSCR Working Group advising on revised guidelines for stem cell research and clinical translation
Geographic Reach Multiple continents/international 
Policy Influence Type Participation in a advisory committee
URL https://www.isscr.org/docs/default-source/all-isscr-guidelines/guidelines-2016/isscr-guidelines-for-...
 
Description Member of NC3Rs Impact Working Group
Geographic Reach National 
Policy Influence Type Membership of a guideline committee
 
Description Member of National Academies/Royal Society Commission on Clincal Use of Human Germline Genome editing
Geographic Reach Multiple continents/international 
Policy Influence Type Participation in a advisory committee
URL https://royalsociety.org/topics-policy/projects/genetic-technologies/international-commission/
 
Description Member of Nuffield Council on Bioethics
Geographic Reach National 
Policy Influence Type Participation in a advisory committee
URL http://nuffieldbioethics.org
 
Description Member of Nuffield Council on Bioethics Working Group on Genome Editing in Farmed Animals
Geographic Reach Multiple continents/international 
Policy Influence Type Participation in a advisory committee
URL http://nuffieldbioethics.org/project/genome-editing-farmed-animals
 
Description Membership of HFEA Scientific and clinical advances advisory committee and Chair of License Committee
Geographic Reach National 
Policy Influence Type Participation in a advisory committee
Impact Contribution to HFEA's policy on regulating research involving the use of animals containing human material (ACHM) and the justification for using human embryos in research. In 2013 I became chair of the HFEA's License Committee. The License Committee licenses all treatment and storage facilitates for ART in the UK and all research establishments using human embryos for research. In January 2016 I chaired the committee that granted the first license to a UK laboratory aiming to use genome editing in human embryos.
 
Description Capital Equipment
Amount £200,000 (GBP)
Organisation Medical Research Council (MRC) 
Department Medical Research Foundation
Sector Charity/Non Profit
Country United Kingdom
Start 10/2013 
End 11/2013
 
Title Gadd45g role in testis determination 
Description We reported a novel link in 2012 between GADD45g, a protein previously implicated in cellular stress response and DNA repair, and testis determination in mice. This has opened up new entry points into studying the mechanism of testis determination, especially the regulation of expression of SRY, in mouse and humans. 
Type Of Material Model of mechanisms or symptoms - mammalian in vivo 
Provided To Others? No  
Impact A publication in Developmental Cell 
 
Title Identification of the boygirl (byg) mutant 
Description We have generated a mouse mutant (byg) exhibiting defects of embyonic gonad development due to disruption of MAP3K4, a gene involved in MAPK signaling. This has allowed us to investigate a novel entry point into the molecular genetic control of sex determination. We are attemtping to apply this knowledge to understanding human disorders of sexual development. This discovery has had a major impact in the field. 
Type Of Material Model of mechanisms or symptoms - mammalian in vivo 
Provided To Others? No  
Impact We used our knowledge of the role of MAPK signalling in mouse sex determination to accelerate progress in a project describing a human disorder of sex development caused by mutations in a related human gene, MAP3K1. This study was published in Am.J.Hum.Genet. and generated considerable publicity. See also http://perspectives.mrc.ac.uk/chapters/cells-genes-and-molecules#achievement-4 
 
Description MAPK signaling in mouse sex determination 
Organisation Institute for Research in Biomedicine (IRB)
Department Signalling and Cell Cycle Laboratory (Oncology)
Country Spain 
Sector Academic/University 
PI Contribution We collaborated with the lab of Prof. Angel Nebreda to assess the role of p38 MAPK signalling in mouse testis determination. With Dr McElreavey at the Institut Pasteur we are using mouse genetics to shed light on causes of disorders of sex development (DSD) in the human population. We are collaborating with Prof. Edward Tobias (University of Glasgow) to make a mouse model of a genetic defect found in patients with a DSD.
Collaborator Contribution Our partners were able to supply important mouse mutant material for us to examine. Dr McElreavey provides us with data concerning gene mutations in patients with DSD. We are modelling these mutations in mouse using different mutagenesis techniques, including CRISPR/Cas9. Prof. Tobias has shared with us genetic data concerning a case of human DSD
Impact A manuscript describing our research was published in Developmental Cell. Both myself and Dr. McElreavey are on the steering committee for the EU COST Action, DSDnet. We jointly chair the Genetics and Biology working group. Prof. Tobias is also a DSDnet member. We will seek EU funding to support collaborations with workers in Europe studying DSD, using DSDnet as a locus for interaction.
Start Year 2011
 
Description MAPK signaling in mouse sex determination 
Organisation Pasteur Institute, Paris
Department Human Evolutionary Genetics
Country France 
Sector Academic/University 
PI Contribution We collaborated with the lab of Prof. Angel Nebreda to assess the role of p38 MAPK signalling in mouse testis determination. With Dr McElreavey at the Institut Pasteur we are using mouse genetics to shed light on causes of disorders of sex development (DSD) in the human population. We are collaborating with Prof. Edward Tobias (University of Glasgow) to make a mouse model of a genetic defect found in patients with a DSD.
Collaborator Contribution Our partners were able to supply important mouse mutant material for us to examine. Dr McElreavey provides us with data concerning gene mutations in patients with DSD. We are modelling these mutations in mouse using different mutagenesis techniques, including CRISPR/Cas9. Prof. Tobias has shared with us genetic data concerning a case of human DSD
Impact A manuscript describing our research was published in Developmental Cell. Both myself and Dr. McElreavey are on the steering committee for the EU COST Action, DSDnet. We jointly chair the Genetics and Biology working group. Prof. Tobias is also a DSDnet member. We will seek EU funding to support collaborations with workers in Europe studying DSD, using DSDnet as a locus for interaction.
Start Year 2011
 
Description MAPK signaling in mouse sex determination 
Organisation University of Glasgow
Country United Kingdom 
Sector Academic/University 
PI Contribution We collaborated with the lab of Prof. Angel Nebreda to assess the role of p38 MAPK signalling in mouse testis determination. With Dr McElreavey at the Institut Pasteur we are using mouse genetics to shed light on causes of disorders of sex development (DSD) in the human population. We are collaborating with Prof. Edward Tobias (University of Glasgow) to make a mouse model of a genetic defect found in patients with a DSD.
Collaborator Contribution Our partners were able to supply important mouse mutant material for us to examine. Dr McElreavey provides us with data concerning gene mutations in patients with DSD. We are modelling these mutations in mouse using different mutagenesis techniques, including CRISPR/Cas9. Prof. Tobias has shared with us genetic data concerning a case of human DSD
Impact A manuscript describing our research was published in Developmental Cell. Both myself and Dr. McElreavey are on the steering committee for the EU COST Action, DSDnet. We jointly chair the Genetics and Biology working group. Prof. Tobias is also a DSDnet member. We will seek EU funding to support collaborations with workers in Europe studying DSD, using DSDnet as a locus for interaction.
Start Year 2011
 
Description Cafe Scientifique 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Public/other audiences
Results and Impact At an evening Cafe Scientifique in Wallingford (Oxfordshire) I discussed the science and ethics of mitochondrial donation
Year(s) Of Engagement Activity 2016
 
Description Chair of panel discussion at Festival of Genomics 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Public/other audiences
Results and Impact I chaired a panel discussion at the London Festival of Genomics entitled: "Genome editing: a precision tool for medicine?"
Year(s) Of Engagement Activity 2018
URL http://www.frontlinegenomics.com/opinion/18677/watch-festival-genomics-london-2018/
 
Description Chaired debate on "The Culture of Scientific Research in the UK" at Oxford Brookes University (Sept 2014) 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? Yes
Geographic Reach National
Primary Audience Other academic audiences (collaborators, peers etc.)
Results and Impact Around 80 people attended a workshop in Oxford - the output of this and other workshops nationally will be included in an NCOB report.

Launch of the findings of a series of engagement activities exploring the culture of scientific research in the UK:
Thursday 4 December 2014, 14.00-15.30 (lunch from 13:30)
The Jubilee Room, Palace of Westminster
Year(s) Of Engagement Activity 2014
URL http://nuffieldbioethics.org/project/research-culture/
 
Description Didcot Sixth Form College Event 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Schools
Results and Impact I gave a talk to sixth formers at a local school (Didcot) on the topic of the science of embryology, genome editing, mitochondrial donation, pre-clinical research with animals and policy/ethics issues in biotechnological innovation. I have given similar talks at other local schools.
Year(s) Of Engagement Activity 2016
 
Description Discussing bioethics with school children 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Type Of Presentation Keynote/Invited Speaker
Geographic Reach Local
Primary Audience Schools
Results and Impact Over three separate visits around 150 16-year-old pupils took part in a discussion of ethics and ethical debate in scientific research - primarily concerning the use of animals in medical research. The sessions were animated and interactive and enjoyed by all.

The school were delighted with the way the discussions fed into the pupils' curriculum-based work. An invitation back next year seems likely.
Year(s) Of Engagement Activity 2011
 
Description Hosted Ethical Debate at MRC Harwell 
Form Of Engagement Activity Participation in an open day or visit at my research institution
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Schools
Results and Impact I hosted an ethical debate at MRC Harwell with year 10 school children from King Alfred's school on the the ethics of Animal Research


None
Year(s) Of Engagement Activity 2010
 
Description Lecture on Ethics at Imperial College 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Type Of Presentation Keynote/Invited Speaker
Geographic Reach Regional
Primary Audience Other academic audiences (collaborators, peers etc.)
Results and Impact This was a presentation on ethics and animal research that I was invited to give by Imperial College, University of London. It was considered to be a part of the refresher training required by individuals at Imperial using animals in research. Attendance was registered.

The lecture was attended by the Dean of the Faculty of Natural Sciences at IC. I had positive feedback from attendants. It is unclear if it will be a regular appearance.
Year(s) Of Engagement Activity 2013
 
Description Oxford Martin School Event 
Form Of Engagement Activity A formal working group, expert panel or dialogue
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Public/other audiences
Results and Impact I was invited to sit on an expert panel in order to discuss the proposition: "Gene editing revolution: should there be limits?" The meeting was held at the Oxford Martin School and hosted by philosopher, Julian Savulescu. Other participants included Robin Lovell-Badge and Alison Murdoch.
Year(s) Of Engagement Activity 2016
URL http://www.oxfordmartin.ox.ac.uk/event/2400
 
Description Oxfordshire Science Festival Event 
Form Of Engagement Activity A formal working group, expert panel or dialogue
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Undergraduate students
Results and Impact The event was entitled "Is genetic engineering of humans ethically justified?" I was part of a panel of experts, answering questions from the audience concerning the science, policy and ethics of genome editing in humans
Year(s) Of Engagement Activity 2016
URL https://www.facebook.com/events/1800019693562222/
 
Description Progress Educational Trust Annual Conference 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Professional Practitioners
Results and Impact I gave a talk entitled 'Carry On Editing' aimed at discussing the importance of genome editing as a tool in basic research - and covering aspects of the ethics of germ line interventions. I was subsequently requested to submit a written version of my talk to the British Medical Bulletin.
Year(s) Of Engagement Activity 2017
URL https://www.progress.org.uk/conference2017
 
Description RSPCA lay member's forum 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Professional Practitioners
Results and Impact I was invited by Penny Hawkins of the RSPCA to speak at an event held at the Royal Society. The theme of the day was the role of AWERBs in regulating animal research establishments. My talk was entitled "Putting ethics into the AWERB". A number of people in the audience that day subsequently contacted me to invite me to speak at their own establishments on this topic.
Year(s) Of Engagement Activity 2016
URL https://science.rspca.org.uk/sciencegroup/researchanimals/ethicalreview/differentsystems/uk/events
 
Description Religion & Science - school visit 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? Yes
Type Of Presentation Keynote/Invited Speaker
Geographic Reach Regional
Primary Audience Schools
Results and Impact I gave a presentation, as part of a day of activities, concerning the nature of scientific explanation and its historical role.

Informal feedback that the day was much enjoyed by pupils.
Year(s) Of Engagement Activity 2012
 
Description Royal Society Events 
Form Of Engagement Activity A formal working group, expert panel or dialogue
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Policymakers/politicians
Results and Impact I was invited to a dinner hosted by Venki Ramakrishnan at the Royal Society to discuss the theme: "Cultural implications of the applications of genetic technologies". It was attended by several other invited contributors from diverse backgrounds (including the author Kazuo Ishiguro) and personnel from the Royal Society policy team.
This resulted in me being invited to be a speaker at a subsequent Royal Society's Scientific Policy Advisory Group dinner, in order to discuss "The future of genetic technologies: regulation, culture and ethics". The dinner was hosted by Ottoline Leyser.
Year(s) Of Engagement Activity 2016
 
Description Royal Society of Medicine Event 
Form Of Engagement Activity A formal working group, expert panel or dialogue
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Professional Practitioners
Results and Impact I was invited to join an expert panel at a RSM meeting entitled "Gene editing in medicine: breakthrough or thin end of the wedge?" The panel discussed the proposition: "This house believes embryonic gene editing will improve the health of future generations."
Year(s) Of Engagement Activity 2016
URL https://www.rsm.ac.uk/events/events-listing/2016-2017/sections/medical-genetics-section/mgh02-gene-e...
 
Description STEM Ambassador Visits 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Schools
Results and Impact I have attended two STEM ambassador functions in the last year over at Rutherford Appleton Library. One was called What's My Line? - students from five local schools had to look at the clues I had taken and work out what sort of job I did. The second event was with a large group of teachers, from Oxfordshire schools. I told them about my research and made links.

None
Year(s) Of Engagement Activity 2009,2010
 
Description Sex and gender forum 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Undergraduate students
Results and Impact I was part of a panel discussing sex, gender and identity from a number of perspectives. We answered questions from the floor. It was held in Oxford.
Year(s) Of Engagement Activity 2016
URL https://www.facebook.com/events/1715859145320587/
 
Description Talk at APHA "Ethics and Welfare" day 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Professional Practitioners
Results and Impact I gave a talk at APHA (Surrey) entitled "Ethics and animal research" in order to stimulate discussion concerning the justification for the sue of animals in research.
Year(s) Of Engagement Activity 2017
 
Description Talk at EMBL 'Science & Society' Symposium - Rewriting the Code of Life: Benefits and Risks 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Public/other audiences
Results and Impact I gave a talk entitled "From blunt instrument to precision tool? The history and future of genetic modification" - as part of a Science and Society symposium hosted by EMBL to inform and generate debate with wider publics.
Year(s) Of Engagement Activity 2017
URL https://www.embl.de/external/events/2017/SNS17-01/programme/index.html
 
Description Talk at Leopoldina, Halle, Germany 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Policymakers/politicians
Results and Impact I was invited to give a talk at the annual assembly of the Leopoldina entitled "Human embryo genome editing: regulation and ethical perspectives". The focus of the meeting was genome editing - and how Germany might benefit from it in a variety of contexts.
Year(s) Of Engagement Activity 2017
URL http://www.leopoldina.org/en/events/event/event/2449/
 
Description Talk at PET/Genetic Alliance meeting in London 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Patients, carers and/or patient groups
Results and Impact I gave a talk entitled "Genome editing in humans" to a group of patient group representatives and members of the general public on the topic of genome editing. This was part of a series of events, funded by the Wellcome Trust, aimed at gauging knowledge, about and attitudes to, genome editing (https://www.progress.org.uk/genomeediting).
Year(s) Of Engagement Activity 2017
URL https://www.progress.org.uk/genomeediting
 
Description Talk to 6th form at Magdalen College School, Oxford 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Schools
Results and Impact A talk to the MCS 6th form about the science and ethics of genetic modification in humans and animals
Year(s) Of Engagement Activity 2018
 
Description Visit to Abingdon School 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Schools
Results and Impact I gave a talk to A level biology students on the topic of mitochondrial replacement techniques - covering the science and ethical issues.
Year(s) Of Engagement Activity 2015