Collaborating to find novel regenerative treatments for disease.
Alasdair G Rooney1 & Jennifer Easterbrook2
1PhD student, MRC/MRF ‘Psychiatric Specialty Training in Academic Research’ (PsySTAR) programme, MRC Centre for Regenerative Medicine, University of Edinburgh, Royal Infirmary of Edinburgh, Edinburgh, Scotland, EH16 4UU, UK; [email protected]
2PhD student, Wellcome Trust ‘Edinburgh Clinical Academic Training’ (ECAT) programme, MRC Centre for Regenerative Medicine, University of Edinburgh, Royal Infirmary of Edinburgh, Edinburgh, Scotland, EH16 4UU, UK
BIRAX (the Britain/Israel Research and Academic Exchange Partnership)  is a £10 million initiative of the British Council and British Embassy in Israel, originating in collaboration with the Pears Foundation  and the United Jewish Israel Appeal (UJIA) . The initiative incentivises basic and clinical scientists in Britain and Israel to collaborate in tackling some of the world’s most challenging diseases including cardiovascular, liver and neurodegenerative diseases, and diabetes. In support of these aims, world-leading medical research charities that have recently joined the BIRAX programme include Alzheimer’s Drug Discovery Foundation, Alzheimer’s Society, Arthritis Research UK, the British Heart Foundation, JDRF, the MS Society and Parkinson’s UK. Since launching in 2008 BIRAX has completed two funding calls and supported a total of 15 world-class projects in the field of stem cells and regenerative medicine . The third call for proposals is currently open and further details of this can be found at the end of the article.
The third BIRAX Regenerative Medicine Conference was held 11—12 April 2016 in Oxford (UK), in association with the Oxford Stem Cell Institute. This was the first time the event has been held in the UK (two previous conferences being held respectively in Beersheba and Haifa, Israel). Over 300 delegates from the UK and Israel enjoyed a wide-ranging scientific programme with sessions covering developmental stem cell biology, immunology and immunotherapy, gene therapy, bioengineering, stem cell reprogramming, epigenetics, nanotechnology, and translation of these areas to the clinic.
Although together these sessions contributed to the overall conference theme of ‘regenerative medicine’, what makes BIRAX unique is the opportunity it provides for synergistic collaboration between UK and Israeli scientists. Examples of such collaboration were featured in a series of updates from active and ongoing BIRAX projects. While there is not space here to list them all, a few can be highlighted with the aim of giving a flavour of what distinguishes the BIRAX initiative from others in the field of regenerative medicine.
One such collaborative talk was entitled “Regenerative cell therapy for Parkinson’s disease: microparticle delivery system for promoting the survival and integration of ESC-derived neuronal grafts”. Here, Dr Sharona Even-Ram (Hebrew University of Jerusalem, Israel) initially described her lab’s work towards the production of dopaminergic neurons from embryonic stem cells. She stressed how topography, dimensionality and compliance all make a difference in tissue culture. Her BIRAX collaborator Prof. Kevin Shakesheff (University of Nottingham, UK) then described the ongoing efforts in his laboratory to optimise the microenvironment for delivery of the ESC-derived dopaminergic neurons, such as by using nanoparticles to which neurons can adhere and be delivered via injection. By leveraging the skills of each lab in collaboration, the researchers hope to transplant mature neurons that are more likely to survive, maintain functionality and restore innervations to the diseased brain.
Another example of BIRAX-funded collaboration was provided in a talk entitled “Production of metabolically functional human pluripotent stem cell-derived hepatocytes”. Here, Prof. Stuart Forbes (University of Edinburgh, UK) and Prof. Yaakov Nahmias (Hebrew University of Jerusalem, Israel) have linked up to address a common problem in stem cell biology: the difficulty of ensuring that replacement cells are sufficiently mature as to have adult levels of functional capability. Prof. Nahmias presented unpublished data suggesting that microbiome-derived cues may help activate later stages of hepatocyte metabolic maturation. Using these insights the researchers aim to drive the generation of the first fully functional, human induced pluripotent stem cell-derived hepatocyte, focusing initially on predictive toxicology applications.
Other collaborations were at an earlier stage and reported on progress during the first year of a project. For example (and as one of several projects that focused on developing regenerative therapies for diabetes) BIRAX recipient Prof. Neil Hanley (University of Manchester, UK) gave a talk entitled “Epigenomics and transcriptomics of human pancreatic beta-cell differentiation and ageing”. He outlined a strategy, working in collaboration with Prof. Ben Glaser (Hebrew University, Israel), to scrutinise why developing beta cells are more proliferative than adult cells. The scientists aim to build an epigenetic map of beta cell development and ageing over the human lifespan. Their goal is to learn how to make adult beta cells proliferate and thereby increase the functional mass available for therapeutic applications.
Although BIRAX focuses primarily on collaborations between established PIs, it also aims to support early career researchers. To this end registration for and accommodation during the conference were, very generously, free. Travel bursaries were also available for junior researchers. These things doubtlessly contributed in part to healthy attendance at a ‘Students and Young Researchers’ Symposium’ on the morning of the second day. The Symposium was ably chaired by Prof. Chris Denning (University of Nottingham, UK) and Dr Jo Beall (British Council Director of Education) and gave 12 PhD students/postdoctoral researchers the chance to present their research in 10-minute slots. Here again cutting-edge science was on display and topics ranged widely, from developing autologous patient-specific implants derived from omentum (Reuven Edri, Tel Aviv University, Israel) to using airway stem cells in tracheal tissue engineering (Robert Hynds, UCL, UK); from unpicking the role of microRNAs in human pericardial fluid (Cristina Beltrami, University of Bristol) to developing optogenetic control of iPSC-derived cardiomyocytes (Amit Gruber, Technion Institute, Israel).
Again some collaborative projects were on show, including a striking example from Martina de Majo (a PhD student at King’s College London, UK, working in the laboratory of Prof Christopher Shaw). She described a project that combines UK-based DNA exon sequencing and expertise in the biology of motor neuron disorders with clinical access in Jerusalem (via Dr Marc Gotkine, Hadassah Medical Center, Israel) to a Palestinian family with a high incidence of amyotrophic lateral sclerosis (ALS). This collaboration uncovered a novel homozygous mutation in the Optineurin gene that was absent in >70 000 controls and confirmed using genotyping of patient-derived fibroblasts. Ms de Majo described future plans to generate induced pluripotent stem cells from the case to further investigate the disease mechanism.
Science & industry
The Young Researchers’ Symposium was directly followed by a question and answer-style session in which audience questions were fielded by a panel of researchers drawn from the UK and Israel. The panel encompassed a range of backgrounds and experience, from post-doctoral level to those edging closer to contemplating life as ‘Professors Emeritus’. After a warm-up run through ‘the toughest part of your career’ (answers included securing funding and recognition, balancing time pressures, and establishing yourself as an independent PI), the young audience homed in on grilling the panel on their views of the relationships between science and industry. Sequential questions included “Did anyone consider going into industry?”, “Do you know any researchers who went into industry and then returned to academia?”, and “Can you suggest anything that would help us to make the transition to starting our own companies?”
In response the panel gave measured advice stressing the importance of: being clear as to how job decisions fit within a long-term strategic career plan; sounding out how the company might approach the publication of results; and avoiding spreading oneself too thinly. Somewhat controversially there was disagreement as to whether, in general, scientists make successful entrepreneurs. Panel suggestions ranged from one extreme (going into partnership with someone who has better business skills), to the other (finding a ‘DIY’ programme that teaches you those skills), before alighting on the sensible conclusion that the most important thing of all is to decide what you want to do most, and then focus on making it happen. More generally this line of questioning, adopted without prompting by the audience, served to highlight a key emerging strength of the BIRAX initiative, namely its focus on the novel application of technology, biomaterials, and tissue engineering to the development of novel regenerative therapeutic strategies.
The hope, as Prof. Chris Mason (Professor of Regenerative Medicine Bioprocessing at UCL, UK) states, is that bringing together world-leading scientists from Israel and the UK “will accelerate cures and transformative therapies for a number of serious conditions that impact the lives of millions of patients and their carers” . Trevor Pears (Executive Chair of the Pears Foundation) concurs: “BIRAX has become a key platform in advancing knowledge and treatment of some of the most challenging global health issues while facilitating lasting relationships between Israeli and British scientists” .
The third BIRAX call for funding is now open with a deadline for preliminary proposals of 12th May 2016. Details of the call, including guidelines and frequently asked questions, can be accessed here: https://www.britishcouncil.org.il/en/third-birax-research-call.
- BIRAX website: www.britishcouncil.org.il/en/birax2015/about
- Pears Foundation website: www.pearsfoundation.org.uk
- United Jewish Israel Appeal website: https://ujia.org
- Currently funded BIRAX projects: www.britishcouncil.org.il/en/birax2015/projects
- Pears T. Foreword. In: BIRAX 3rd Regenerative Medicine Conference Programme. British Council, UK, page 3 (2016).
If you are interested in reading more, Alex Brookes, Head of BIRAX and Higher Education at the British Council (UK), discusses the importance of the BIRAX programme in accelerating the development of regenerative medicine therapies in an interview with RegMedNet.