Molecular Genetics of Sex Determination, the Sox Gene Family and Stem Cell Biology

Lead Research Organisation: MRC National Inst for Medical Research

Abstract

Embryonic cells, and adult stem cells, have alternate fates where they can stay unspecialised, adopt one or more differentiated states, or die. This project is concerned with how these decisions are made, and in doing so we focus both on normal situations and on situations when these the decisions go awry, such as with congenital and chromosomal abnormalities, physiological stress and trauma, and in cancer and ageing. We follow two general approaches. The first explores the roles of the SOX genes, which encode transcription factors that play pivotal roles during cell fate decisions. The second involves studying the cellular and molecular interactions required to establish and maintain specific systems. For example, we study how the embryo becomes male or female. This decision takes place in the early embryo and leads to the gonads becoming testes (if the embryo has a Y chromosome carrying a gene called Sry) or ovaries (if it does not). This is a paradigm of how cell fate decisions are made, and our work has led not only to an understanding of the mechanisms involved, but also to better diagnosis, counselling and treatment of disorders of sex differentiation in humans. We also research brain stem cells, where it is necessary to understand how SOX proteins function within them, but also to appreciate the effect of the stem cell environment. Our improved understanding of cell fate decisions may allow us to control them in a beneficial way for treatment of human and animal disease and trauma.

Technical Summary

The overall aims of our research are to provide basic understanding of how decisions of cell fate are reached during the development of the vertebrate embryo, how these decisions are maintained or continue to be made in the adult, what happens when they go wrong and how they might be manipulated in such ways as to provide therapeutic benefit. Such decisions of cell fate are critical for the organisation of the basic body plan as well as for development of specific organs and tissues. They are also important for homeostasis of the adult, particularly with respect to stem cells and their ability to self-renew or differentiate. Many of the genes we study function at different stages and in multiple sites, and even if they act in the embryo, they can have consequences for the resulting animal in terms of anatomy, physiology and behaviour. It is therefore important to cover a range of systems and stages to reveal general principles and to understand how they act on cell fate decisions and exert pleiotropic effects on development, homeostasis and disease. More specifically we seek to understand: (i) sex determination and differentiation, (ii) the establishment of cell lineages in the early (pre- and post-implantation) embryo, (iii) aspects of CNS development, maintenance and function, especially those involving stem cells, (iii) pituitary development and plasticity, (iv) the role of specific Sox genes in the development of sensory systems such as the ear and other organs where they have critical roles, and (v) the role of specific Sox genes and stem cells in cancer and ageing. In addition to the intrinsic benefit of understanding how animals and humans develop and function, our work will provide valuable information that can be used in clinical diagnosis and management of patients, and towards developing treatments for a range of problems associated with disease and trauma. For example, our work on sex determination, has already revealed several genetic causes of sex reversal, intersex conditions, and infertility; more will be discovered and we can now even envisage the possibility of treatment in some cases. Our work on the pituitary has lead to better management of patients with defects in the genes we study, and it may lead to better ways to regulate aspects of the physiology it controls. Our work on CNS and sensory system development will lead to better understanding of congenital disease. We hope that our understanding of how stem cells behave in both normal and diseased situations will ultimately benefit approaches for their use in regenerative medicine, whether these depend on cell transplantation or their manipulation in vivo, or in developing ways to treat cancer or overcome aspects of ageing. For example, we are part of a collaborative study, partly funded by the NIH, to directly explore the use of neural stem cells and components of their niche in treating stroke. We are currently also exploring with MRCT, screening small molecule libraries for antagonists that prevent Sox9 activating a target oncogene.

Publications

10 25 50

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Bagheri-Fam S (2012) Sox9 gene regulation and the loss of the XY/XX sex-determining mechanism in the mole vole Ellobius lutescens. in Chromosome research : an international journal on the molecular, supramolecular and evolutionary aspects of chromosome biology

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Balkwill F (2011) Safety of medicines and the use of animals in research. in Lancet (London, England)

 
Description Co-organiser, Co-chair, speaker and discussant for FEAM meeting on Human Genome Editing, held in Paris on 28 April 2016.
Geographic Reach Multiple continents/international 
Policy Influence Type Participation in a advisory committee
URL http://www.feam-site.eu/cms/docs/humangenomeeditingworkshop2016report.pdf
 
Description Council member for Understanding Animal Research (UAR).
Geographic Reach Asia 
Policy Influence Type Participation in advisory committee
Impact UAR defends research on animals and the scientists and Institutions involved. Without animal research there would be little progress in aspects of basic science, in medicine, veterinary practice, etc, etc, and the UK economy would be harmed.
 
Description Elected to the Council of the Royal Society
Geographic Reach Multiple continents/international 
Policy Influence Type Participation in advisory committee
Impact Multiple impacts - although it is difficult to measure the extent in most cases and I cannot take credit for all of this - we worked as a team and were led by the "Officers", etc.
URL http://www.royalsociety.org/
 
Description Hfea: Scientific review of the safety and efficacy of methods to avoid mitochondrial disease through assisted conception
Geographic Reach Multiple continents/international 
Policy Influence Type Membership of a guidance committee
URL http://www.hfea.gov.uk/6372.html
 
Description Hinxton Group meeting and consensus statement: Proprietary Challenges in Stem Cell Research
Geographic Reach Multiple continents/international 
Policy Influence Type Membership of a guidance committee
URL http://www.hinxtongroup.org/
 
Description House of Commons S&T Select Committee on Government Proposals on the Regulation of Hybrid and Chimera Embryos.
Geographic Reach National 
Policy Influence Type Gave evidence to a government review
Impact The report of this Committee helped to influence a change of Government thinking on the issue. Previously they had proposed to ban this type of research, but my evidence along with that of others, began to lead to a more permissive attitude. This eventually led to the type of research being permitted in the HFE Act (2008)
 
Description House of Commons S&T Select Committee on Research Council Institutes
Geographic Reach National 
Policy Influence Type Gave evidence to a government review
 
Description Individual advice to the HFE Bill Team and to Parliamentarians
Geographic Reach Multiple continents/international 
Policy Influence Type Gave evidence to a government review
Impact I was called on frequently in 2007 and 2008 to provide scientific advice to the team drafting the HFE Bill and to individual MPs and Peers. I believe I had some direct influence from these efforts, in addition to the other routes. N.B. Because many other countries look to the UK for how to regulate in this area of science and clinical practice, the influence is wider than just the UK.
 
Description Joint Committee on the Draft Human Tissue and Embryos Bill
Geographic Reach Multiple continents/international 
Policy Influence Type Gave evidence to a government review
Impact The Report of this Committee, based on my evidence and that of others, led to a complete revision of the Governments original plans to have restrictive legislation on research involving "human admixed embryos" and to merge the HTA and the HFEA, etc. N.B. Because many other countries look to the UK for how to regulate in this area of science and clinical practice, the influence is wider than just the UK.
 
Description Mitochondrial Donation
Geographic Reach Multiple continents/international 
Policy Influence Type Gave evidence to a government review
 
Description Mitochondrial Donation Regulations
Geographic Reach National 
Policy Influence Type Gave evidence to a government review
Impact The Mitochondrial Donation Regulations were adopted into law as an amendment to the HFE Act (2008).
 
Description Mitochondrial Donation Regulations
Geographic Reach National 
Policy Influence Type Implementation circular/rapid advice/letter to e.g. Ministry of Health
Impact The Mitochondrial Donation Regulations were adopted into law as an amendment to the HFE Act (2008).
 
Description NAS Study Committee on Human Genome Editing
Geographic Reach Multiple continents/international 
Policy Influence Type Participation in a advisory committee
URL http://nationalacademies.org/gene-editing/
 
Description Talk and discussion with the French National Ethics Advisory Board on life sciences and health (CCNE), Paris. 27 April, 2016
Geographic Reach Europe 
Policy Influence Type Participation in a national consultation
URL http://www.ccne-ethique.fr/en
 
Description The "Gang of four" policy group
Geographic Reach Multiple continents/international 
Policy Influence Type Participation in advisory committee
Impact I was one of two scientific experts, and the most directly relevant, on this small group of mostly policy and law experts from the MRC, the Academy of Medical Scientists, the Wellcome Trust and the Royal Society (and occasionally the Association of Medical Research Charities) that had been assembled to monitor the debates as the HFE Bill progressed through Parliament, to provide information to Parliamentarians and the Government, writing briefing documents and drafting amendments. The efforts of this group had an enormous influence on many aspects of the HFE Act (2008). N.B. Because many other countries look to the UK for how to regulate in this area of science and clinical practice, the influence is wider than just the UK.
 
Description The Academy of Medical Sciences Report on: "Animals Containing Human Material"
Geographic Reach Multiple continents/international 
Policy Influence Type Membership of a guidance committee
Impact Although centered on UK policy, this Report is likely to have an international impact. It is too early to say how extensive this will be, but our recommendations will form part of the UK's plans as to how to adopt to the EU Directive on Animals in Research. It has also led to an agreement by the Department of Health, Home Office, and the HFEA, to jointly consider research that falls into category II of our proposed types of research involving ACHM. The Report has been read widely and was met with much interest and enthusiasm.
URL http://www.acmedsci.ac.uk/viewFile/5256617151991.jpg
 
Description The Academy of Medical Sciences Working Group on Interspecies Embryos
Geographic Reach Multiple continents/international 
Policy Influence Type Membership of a guidance committee
Impact The report of this Working Group (http:www.acmedsci.ac.uk/p99.html) was very influential both to the various Select Committees considering the HFE Bill, directly to Government and to the team drafting the Bill. N.B. Because many other countries look to the UK for how to regulate in this area of science and clinical practice, the influence is wider than just the UK.
URL http://issuu.com/acmedsci/docs/11835662253
 
Description The HFE Bill strategy Group
Geographic Reach Multiple continents/international 
Policy Influence Type Participation in advisory committee
Impact This was a large group representing a many organisations concerned with the HFE Bill. It provided briefing documents to Parliamentarians and drafted several amendments. I was one of the few scientists in the Group with relevant expertise. This Group had a clear influence on the shape and details of the HFE Act (2008). N.B. Because many other countries look to the UK for how to regulate in this area of science and clinical practice, the influence is wider than just the UK.
 
Description The Hinxton Group
Geographic Reach Multiple continents/international 
Policy Influence Type Membership of a guidance committee
Impact I am a founder member of this Group and serve on their steering committee, which is responsible for researching a topic, organising an international meeting on the topic, and drafting recommendations on how to improve policy at an international level on aspects of stem cell research and practice. We have now held three meetings, in 2006, 2008, and one just recently in 2010. The reports are available on the Group's website: www.hinxtongroup.org. They have received wide attention in policy circles around the world, and have had an influence on legislation (e.g. with respect to research on pluripotent stem cell-derived gametes, included in the HFE Act (2008).
URL http://www.hinxtongroup.org
 
Description Baylor College Research Grant-2006
Amount £245,606 (GBP)
Organisation Baylor College of Medicine 
Sector Hospitals
Country United States
Start 01/2006 
End 12/2010
 
Description EU-Marie Curie Fellowship (EIF)-FP6-2006
Amount £115,881 (GBP)
Organisation Marie Sklodowska-Curie Actions 
Sector Academic/University
Country Global
Start  
 
Title Pituispheres 
Description We improved on methods to derive and culture stem/progenitor cells from the pituitary, as so-called pituispheres, and to promote their differentiation into hormone cell types in vitro. 
Type Of Material Technology assay or reagent 
Year Produced 2008 
Provided To Others? Yes  
Impact The methods and our discovery that Sox2 marks the stem/progenitor cell population in the pituitary, have led to an expansion of work in this field. The original work has been published, but in addition we have had more requests to write reviews on the topic than we can do. The culture methods allow work to be carried out in vitro that previously was possible only in vivo (3R's). 
 
Title Sox2 mutant mice 
Description We discovered that Sox2 heterozygous mutant mice exhibit defects in the hypothalamic-pituitary axis (HPA). 
Type Of Material Model of mechanisms or symptoms - mammalian in vivo 
Year Produced 2006 
Provided To Others? Yes  
Impact The mouse data prompted studies in humans carrying SOX2 mutations and led to the discovery that such individuals also have HPA defects. Appropriate treatment for such deficiencies has now been incorporated into the clinical management of such patients. This work was published. The recognition of HPA defects in the mice provided an explanation for their low fertility. This can be improved with hormone treatment (3R's). 
 
Title TESCO-reporter mice 
Description Transgenic mice carrying the testis-specific enhancer of Sox9 linked to reporter genes (e.g. CFP). These provide a simple assay for the effects of factors and gene mutations on sex determination, and can be used for live imaging of early testis development in organ cultures. 
Type Of Material Model of mechanisms or symptoms - mammalian in vivo 
Year Produced 2006 
Provided To Others? Yes  
Impact Several papers from our collaborators and ourselves; others are being prepared for publication. Because they permit live imaging in vitro, this reduces the number of embryos/animals needed for the analysis of events over time (3R's). 
 
Description Sox genes in gastrulation 
Organisation Spanish National Research Council (CSIC)
Country European Union (EU) 
Sector Public 
PI Contribution Our work on the role of Sox2 and Sox3 in epiblast and neuroectoderm meshed very well with their work on Snail genes and epithelial to mesenchymal transition in gastrulation. The work resulted in a very good publication and now a continuing collaboration on the interaction of the two types of gene in other situations.
Collaborator Contribution Their work on Snail genes and epithelial to mesenchymal transition in gastrulation meshed well with ours on the role of Sox2 and Sox3 in epiblast and neuroectoderm. The work resulted in a very good publication and now a continuing collaboration on the interaction of the two types of gene in other situations.
Impact A paper in Developmental Cell (PubMed: 21920318)
Start Year 2010
 
Title Pituitary defects associated with heterozygosity for SOX2 
Description On the basis of our research on mice heterozygous for Sox2 mutations, we teamed up with clinician scientists at the Institute of Child Health, London to show that humans suffering congenital eye disease (ranging to severe forms of anopthalmia) due to mutations in SOX2, also all have pituitary dysfunction. The latter can, and now is be managed by appropriate hormone treatment. 
Type Management of Diseases and Conditions
Current Stage Of Development Wide-scale adoption
Year Development Stage Completed 2008
Development Status Closed
Impact The condition affects only a small number of patients, but whereas they used to be managed only for eye problems, other aspects of their physical and mental well-being due to pituitary deficits are now also being addressed. This is also of importance to their families. 
 
Title SOX3 as a candidate gene for disorders of sex differentiation (DSD). 
Description As part of a collaboration with scientists and clinicians in Australia and the USA, we showed that Sox3 could act as a male determining gene if it was misexpressed in the early developing gonads in mice, and this led to the discovery that about 20% of cases of female to male sex reversal in humans (that are not due to SRY) have genome rearrangements around SOX3. This discovery (published in JCI) has rapidly been adopted as a diagnostic tool. 
Type Diagnostic Tool - Non-Imaging
Current Stage Of Development Wide-scale adoption
Year Development Stage Completed 2011
Development Status Closed
Impact I do not know the number of patients found to date with SOX3 as a likely cause of DSD; we described 3 and several more have now been found. However, apart from SRY, this is the next most common cause of female to male sex reversal, so while still rare (1/50,000) it is significant. 
 
Description Nuffield Council of Bioethics "Roundtable on public dialogue for genome editing policy and regulation", 17 March 2016. 
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 This was a scoping meeting to discuss the timing of public engagement around human genome editing, the types of activity this may involve, etc.
Year(s) Of Engagement Activity 2016
 
Description "Café Scientifique" on "Male/Female/None of the Above" at the Maritime Museum, Hong Kong on 03 October 2016. 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Public/other audiences
Results and Impact This event is one in a series organised in Hong Kong, where I spend several weeks each year. It was well attended and prompted a very lively debate.
Year(s) Of Engagement Activity 2016
 
Description AS-ET lecture on "Editing the genomes of animals and humans: where do we draw the line?", held at Kings College, London, on 19 October 2016. 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Professional Practitioners
Results and Impact AS-ET is a charity supporting training of animal technologists. The majority of the audience were animal technicians, but also some of their partners and colleagues.
Year(s) Of Engagement Activity 2016
 
Description AS-ET lecture on "Editing the genomes of animals and humans: where do we draw the line?", held at the University of Manchester on 30 November 2016. 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Professional Practitioners
Results and Impact AS-ET is an educational charity supporting animal technologists. This was a repeat of a talk given in London on 19 October, also mostly to animal technicians, and to some of their partners and colleagues.
Year(s) Of Engagement Activity 2016
 
Description Academy of Medical Sciences' Report on Animals Containing Human Material 
Form Of Engagement Activity A press release, press conference or response to a media enquiry/interview
Part Of Official Scheme? Yes
Geographic Reach International
Primary Audience Media (as a channel to the public)
Results and Impact We had a Press Briefing at which I was a panel member, and I had separate interviews for print, radio and TV. The media coverage was the largest experienced by the AMS, and there were at least 18 million downloads from the media coverage.

I have been asked to speak about the topic on numerous occasions, to academia and to the public.
Year(s) Of Engagement Activity 2011
 
Description Briefing on Human Genome Editing for the Medical Ethics Committee of the BMA on 17 February 2016. 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Professional Practitioners
Results and Impact The Medical Ethics Committee of the BMA wanted to understand the science behind genome editing and where this might lead with respect to both research and human applications. We also discussed relevant ethical and regulatory issues.
Year(s) Of Engagement Activity 2016
URL https://www.bma.org.uk/about-us/how-we-work/professional-activities/medical-ethics-committee/arm-cha...
 
Description Chair of a roundtable discussion on: "Dolly at Roslin, a collective memory event", on 19 April 2016. 
Form Of Engagement Activity A formal working group, expert panel or dialogue
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Study participants or study members
Results and Impact The event was held at the University of Edinburgh, as part of a science history, sociology study that will be published in 2017.
Year(s) Of Engagement Activity 2016
 
Description Interview for Podcast with Max Sanderson of the Guardian on "Big Unknowns: the future of humanity", 17 August 2016. 
Form Of Engagement Activity A broadcast e.g. TV/radio/film/podcast (other than news/press)
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Media (as a channel to the public)
Results and Impact I was asked to address several issues relating to new technologies, notably genome editing.
Year(s) Of Engagement Activity 2016
URL https://www.theguardian.com/science/audio/2016/aug/21/big-unknowns-what-will-become-of-us-podcast
 
Description Interview for a Russian TV Science Documentary on human genome editing at the Crick Institute, 16 November 2016. 
Form Of Engagement Activity A broadcast e.g. TV/radio/film/podcast (other than news/press)
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Media (as a channel to the public)
Results and Impact I do not know if the programme has been aired, but the interview ranged from the general methods and applications of genome editing to research using the methods that was taking place at the Crick.
Year(s) Of Engagement Activity 2016
 
Description Jamie's Dream School 
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 Two postdoctoral scientists within my lab ran a practical on stem cells for the students in "Jamie's Dream School" a television series.

The series generated considerable interest as aspects were quite controversial.Lord Winston, who ran the session, was very pleased with the two members of my lab and how they engaged with the rather unusual set of students.
Year(s) Of Engagement Activity 2011
 
Description Live broadcast from the Crick; BBC World Service radio interview (with Becky Morelle) on human genome editing, on 19 October 2016. 
Form Of Engagement Activity A press release, press conference or response to a media enquiry/interview
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Media (as a channel to the public)
Results and Impact This was a live broadcast from the Institute to promote aspects of the science that goes on within the building.
Year(s) Of Engagement Activity 2016
 
Description Met with a delegation of French MPs conducting an enquiry into human genome editing on 23 May 2016. 
Form Of Engagement Activity A formal working group, expert panel or dialogue
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Policymakers/politicians
Results and Impact The event was part of an evidence gathering process by this group of French Parliamentarians. I was asked to speak to them generally about human genome editing, the findings of the Hinxton Group and the NAS Summit meeting (both in 2015), and specifically about Kathy Niakan's work.
Year(s) Of Engagement Activity 2016
 
Description Newspaper articles 
Form Of Engagement Activity A magazine, newsletter or online publication
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Public/other audiences
Results and Impact 1. Lovell-Badge, R. (2007). "Dame Anne McLaren". The Independent. 12 July. (http://news.independent.co.uk/people/obituaries/article2758798.ece)
2. Lovell-Badge, R. (2007). Commentary on: 'Watchdog to approve research on human-animal hybrid embryos. The Daily Telegraph, 1 September (page 10).
3. Lovell-Badge, R. (2008). Embryo Bill: For and Against. (My piece, "For" followed by "Against", by the Roman Catholic Archbishop of Birmingham, the Most Rev Vincent Nichols). The Daily Telegraph, 24 March.
[http://www.telegraph.co.uk/news/main.jhtml?xml=/news/2008/03/24/nembryo424.xml]
4. Lovell-Badge, R. (2008). "Debate: Will new stem cell research create monsters?" Daily Mail, 21 May, (One of three letters written to the editor.)
5. Lovell-Badge, R. (2008). "Nature plus nurture does not equal a perfect match". The Times, 6 August. (Accompanying the story about the cloning of the pit bull terrier Booger.)
[http://www.timesonline.co.uk/tol/news/world/asia/article4467088.ece]
6. Lovell-Badge, R. (2010). "High quality research is effectively being vetoed". A commentary in Bionews, an online and web based newsletter, written as a follow-up to a BBC news story.
[http://www.bionews.org.uk/page_54345.asp]
7. Lovell-Badge, R and Wighton, K (2010). "I would drink cloned cow's milk." The Sun 3 August.
[http://www.thesun.co.uk/sol/homepage/features/3079199/Genetic-expert-I-would-drink-cloned-cows-milk.html?OTC-RSS&ATTR=Features]
8. Lovell-Badge, R (2011) "Stem cell scientists will simply switch to U.S. if investment cannot be protected". [Stem cell scientists will simply switch to U.S. if investment cannot be protected." [http://www.dailymail.co.uk/news/article-2050737/Stem-cell-scientists-switch-US-investment-protected.html#ixzz1ezOh9300]
9. Lovell-Badge, R. (2012). Hype, hope and heresy - or why it is bad to eggsaggerate.
Bionews (12 March). [http://www.bionews.org.uk/page_133180.asp]
10. Lovell-Badge, R. (2012). We must fight back over lab animal blockade. New Scientist 15
March. [http://www.newscientist.com/article/dn21590-we-must-fight-back-over-labanimal-
blockade.html]
11. Lovell-Badge, R. (2012). An eggsample of why it is hard to prove a negative. Bionews
(30 July). [http://www.bionews.org.uk/page_163374.asp]
12. Lovell-Badge, R. (2013). Nine out of ten statistics are taken out of context.
http://speakingofresearch.com/2013/01/23/nine-out-of-ten-statistics-are-taken-out-ofcontext/
http://www.understandinganimalresearch.org.uk/news/2013/01/nine-out-of-tenstatistics-
are-taken-out-of-context/
13. Lovell-Badge, R. (2013). How to distort 0.004% of the statistics.
http://www.understandinganimalresearch.org.uk/news/2013/05/how-to-distort-0-004-
of-the-statistics/
http://speakingofresearch.com/2013/05/22/how-to-distort-0-004-of-the-statistics/
14. Lovell-Badge, R. (2014). Mitochondrial replacement: no need for a rethink.
New Scientist, 17 October.
[http://www.newscientist.com/article/dn26400-mitochondrial-replacement-no-needfor-
a-rethink.html?full=true]



Considerable interest in terms of comments,"hits" and letters.
Year(s) Of Engagement Activity 2006,2007,2008,2009,2010
 
Description Numerous 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Public/other audiences
Results and Impact Actively involved in helping to maintain the public dialogue on issues raised initially by the changes to the 1990 Human Fertility and Embryo Act in 2001, through to the final passing of the 2008 HFE Act and beyond. This has been through a range of meetings, workshops, and media opportunities. Many of the issues are still being discussed publicly after the Act was passed. In addition, this has included work overseas to explain to policy makers and the public how research involving human embryos and stem cells is regulated in the UK.
The Academy of Medical Sciences current Working Group on "Animals containing human material" commissioned a public engagement exercise, which was conducted by Ipsos Mori. I was a member of the oversight group responsible for this. Their report has been published and is available on both the Academy and Ipsos Mori websites.
Numerous ad hoc press, radio and TV interviews on subjects of genetics, sex determination, cloning, stem cells, etc. This includes media interviews after talks at meetings in the UK and abroad (e.g. in Hong Kong, India, Brazil and the USA). A regular contributor to the output of the Science Media Centre in terms of Press Releases, Media Briefings and explanatory notes, and to Sense About Science activities and publications. Contributed to various recorded radio and TV programmes on stem cells, cloning and genetics and to several radio and TV debates.
A participant in numerous seminars and debates to general audiences in the UK and abroad on stem cells, embryo research, cloning and genetics, ethics and policy. Various lectures to schoolchildren (and teachers) on subjects of genetics and sex determination, stem cells and cloning.
Talks on communicating science and the media: for example, annually for the NIMR postgraduate training programme, and for the "Voice of Young Science" workshops, organized by NESTA and Sense about Science. Contributor to the Sense About Science "Voice of Young Scientists Media Guide," 2006. Related the 'scientists view' of public engagement at the Science Communications Conference, 22 June, 2009, and involved in a SCOPE project looking at the issues from a sociological viewpointA member of the judging panel for the Association of British Science Writers Awards: 2006. Scientific Consultant for the Y-Theatre Touring Company for their production of "Every breath", a play also about stem cell research and the difficult ethical issues surrounding their derivation and use.



Many
Year(s) Of Engagement Activity 2006,2007,2008,2009,2010
 
Description POSTNOTE on Genome Editing (No. 541, November 2016). 
Form Of Engagement Activity A magazine, newsletter or online publication
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Policymakers/politicians
Results and Impact I contributed to this POSTNOTE on Genome Editing, through talking to the main writer, providing written comments and details, and editing the draft. (N.B. Postnotes are published by the Parliamentary Office of Science & Technology with the aim of informing Parliamentarians on new and relevant topics.)
Year(s) Of Engagement Activity 2016
URL http://researchbriefings.parliament.uk/ResearchBriefing/Summary/POST-PN-0541
 
Description Panel Discussion on "The Science and Ethics of Frankenstein", Bristol Festival of Ideas, 23 April 2016. 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Public/other audiences
Results and Impact This was a debate on new techniques (such as genome editing, chimeras, etc) and how they relate to the themes highlighted in Frankenstein (it was associated with the 200th anniversary of the first draft of the book).
Year(s) Of Engagement Activity 2016
 
Description Panellist for Sense About Science/Voice of Young Scientists "Standing up for Science Media Workshop" held at the Crick on 16 September 2016. 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Study participants or study members
Results and Impact This audience was mostly made up of young researchers who wish to gain an insight into public engagement. It was my prompting that led the event being held at the Francis Crick Institute.
Year(s) Of Engagement Activity 2016
 
Description Recorded interview with Tom Feilden on "Animals Containing Human Material" for BBC R4 Today programme on 18 January 2016. 
Form Of Engagement Activity A broadcast e.g. TV/radio/film/podcast (other than news/press)
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Media (as a channel to the public)
Results and Impact The interview was to highlight the adoption of regulations into law on "Animals Containing Human Material" and to discuss the reasons for this type of research and its regulation.
Year(s) Of Engagement Activity 2016
 
Description Science Media Centre briefing with Kathy Niakan on 13/01/16. 
Form Of Engagement Activity A press release, press conference or response to a media enquiry/interview
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Media (as a channel to the public)
Results and Impact The briefing was to discuss Kathy Niakan's plans for human embryo genome editing research (and to introduce her to the journalists). It received a huge amount of media coverage internationally. The journalists also got to appreciate Kathy's qualities as a careful serious researcher - and as someone not seeking publicity.
Year(s) Of Engagement Activity 2016
 
Description Science Media Centre media briefing on the HFEA Panel's Fourth Scientific review of the safety and efficacy of methods to avoid mitochondrial disease through assisted conception. 30 November 2016. 
Form Of Engagement Activity A formal working group, expert panel or dialogue
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Media (as a channel to the public)
Results and Impact The HFEA Panel on which I have served since its inception published its Fourth and (probably) final Report assessing new methods to avoid mitochondrial disease. The HFEA accepted the recommendations made in the report in full at their next meeting. The HFEA are now able to consider applications for licences to use the methods clinically.
Year(s) Of Engagement Activity 2016
URL http://www.hfea.gov.uk/10559.html
 
Description Science Media Centre media briefing together with Magda Zernicka-Goetz on her research involving culture of postimplantation human embryos, on 04 May 2016. 
Form Of Engagement Activity A press release, press conference or response to a media enquiry/interview
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Media (as a channel to the public)
Results and Impact The briefing was concerned with research showing that it was possible to culture human embryos to about 13 days of development. We discussed the reasons behind the research, and where it might lead, in terms of basic knowledge, potential applications, and future policy options - notably whether the 14 day limit on human embryo research should be extended.
Year(s) Of Engagement Activity 2016
 
Description Speaker and panellist for a TalkScience event on "Replace, Reduce, Refine: Animals in Research", held at the British Library, London, on 13 October 2016. 
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 This was a public debate about research on animals and the notions behind the 3Rs - and beyond.
Year(s) Of Engagement Activity 2016
 
Description Speaker and panellist for a session on "What is Gender ?" at the Battle of Ideas Festival, Barbican, London, on 23 October 2016. 
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 This was a debate held at the annual Festival of Ideas organised by the Institute of Ideas. I was asked to be on the panel to present the science behind sex and gender and to participate in the debate, which ranged from medical to social issues.
Year(s) Of Engagement Activity 2016
URL http://www.battleofideas.org.uk/2016/session/11588#.WMbBrpJszr4
 
Description Talk on "Editing the genomes of animals and humans: where do we draw the line?", for the Highgate Literary Society, London, 15 November 2016. 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Public/other audiences
Results and Impact This was a very well attended meeting of the Highgate literati. There was a lively discussion afterwards.
Year(s) Of Engagement Activity 2016
 
Description Talk on "Gene Editing" at the "New Scientist Live" science festival, Excel, London, 24 September 2016. 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Public/other audiences
Results and Impact About 600 members of the public attended in a space designed for 300. It was a very successful event, as judged by responses from both the audience and the organisers. This was the first time the New Scientist Live event had taken place. There will be more and I have been asked to participate in future events.
Year(s) Of Engagement Activity 2016
 
Description Talk to 6th form students at the Hemel Hempstead School on "Ethics and Stem Cells" on 16 March 2016. 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Schools
Results and Impact This was an invited talk/discussion at a good school in Hemel hempstead with the idea of getting the pupils and teachers to discuss both the science of stem cells and the ethical issues surrounding their use.
Year(s) Of Engagement Activity 2016
 
Description Three talks at the 2011 Cheltenham Science Festival 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? Yes
Geographic Reach National
Primary Audience Public/other audiences
Results and Impact I gave three talks at sessions on: Stem Cells; Transgenic animals; Sex determination and gender. All were well attended and provoked very lively debate.

I had a number of e-mails from audience members, such as several from individuals who were concerned about animal experiments, but after hearing about work on transgenics, they could now see why it was important.
I have also had requests to speak in schools and at other events.
Year(s) Of Engagement Activity 2011
 
Description Two talks on Human Genome Editing at the AAAS meeting in Washington DC on 12 February 2016; one for Journalists and one for the public. 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Public/other audiences
Results and Impact This was carried out as part of my involvement in the NAS Initiative on Human Genome Editing and my role at this two events was to discuss the conclusions of the Summit meeting held in December 2015 in Washington DC. Both these AAAS meetings were very well attended and they prompted a lot of discussion. There was substantial media coverage.
Year(s) Of Engagement Activity 2016
 
Description UAR Interview about animals containing human material 
Form Of Engagement Activity A magazine, newsletter or online publication
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Public/other audiences
Results and Impact UAR recorded this interview for their website, and it was put online to coincide with the launch of the Academy of Medical Sciences' Report on Animals Containing Human Material.

The site has had a large number of "hits".
Year(s) Of Engagement Activity 2011
 
Description Visit to Highgate School 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Schools
Results and Impact A postdoctoral fellow from my lab spoke to Highgate School's "Senior Biology Society" about stem cell research. It was very well attended, and provoked a lot of discussion.

She has been asked to make a repeat visit next year.
Year(s) Of Engagement Activity 2011
 
Description Wellcome Trust Image Awards, judging panel, on 18 October 2016. 
Form Of Engagement Activity A formal working group, expert panel or dialogue
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Public/other audiences
Results and Impact The Image Awards were made public on 15 March 2017. I have been on the judging panel for a number of years and it always gets very good publicity and helps to engage the public with science and methods - both of research and image capture.
Year(s) Of Engagement Activity 2016
URL http://www.wellcomeimageawards.org/2017/
 
Description • Multiple ad hoc media interviews (including several on the Today programme), on topics of human genome editing, mitochondrial replacement techniques, animals containing human material, sex determination and gender, in vitro-derived gametes, the 14 day rule on human embryo research, etc. 
Form Of Engagement Activity A press release, press conference or response to a media enquiry/interview
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Media (as a channel to the public)
Results and Impact These interviews were in response to requests from journalists and media outlets to provide scientific background and my views on the topics being covered.
Year(s) Of Engagement Activity 2016