Centre for Genomic Regulation - a hub for Integrative Biology in Barcelona.

Abstract

Luis Serrano Pubul Barcelona, Catalonia, Spain. Not for a single moment should we neglect viewing the area that has lately been the focus of heated political discussions as one of the most important hubs in European Biomedical Research. The Centre for Genomic Regulation (CRG) is the beating heart of the Barcelona Biomedical Research Park (PRBB), ranking 23rd among the Western European institutes that are active in the health sector (SCIMAGO institutions rankings 2017). The CRG turns 18 this year, counting over 400 scientists from 43 countries, and features 29 research groups and 9 core facilities. It is a nonprofit foundation affiliated with Pompeu Fabra University and is funded by the Catalan Government through the Departments of Economy & Knowledge and Health, the Spanish Ministry of Economy, Industry and Competitiveness, the “la Caixa” Banking Foundation. The CRG aspires to promote excellent and innovative research by combining interdisciplinary basic science with cutting edge “omics” technologies, with a strong focus on genomics. Here, we interview the CRG director, Luis Serrano Pubul, on the priorities and strategic plans of the institute. Serrano, born in Madrid, has a PhD in Cell Biology from the Centro de Biología Molecular (CSIC-UAM) of the Universidad Autónoma de Madrid (1987) and the University of Cambridge (1991). In 1993, he was appointed Head of Group at the European Molecular Biology Laboratory (EMBL), in Heidelberg, Germany, and focused his work on protein folding and design. In 2006, he was appointed Head of the EMBL Structural & Computational Biology programme and began to work on Systems Biology. In 2006, he was also named Head of programme at the Spanish National Cancer Research Centre (CNIO). At the end of 2006, he moved back to Spain to direct the Systems Biology programme at the Centre for Genomic Regulation (CRG), where he also served as Deputy Director until his appointment as Director in mid 2011. Currently, his research group focuses on synthetic biology, the engineering and design of biological systems. The Centre for Genomic Regulation. In my view, an approach towards Integrative Biology should entail both the establishment of close collaborations among scientists from distinct disciplines and the fostering of core facilities that can produce and merge large-scale data based on various technologies. Integrative Biology, as an approach, may be followed at both the institute and research group level. For example, in my group, we study the biology of Mycoplasma pneumoniae by performing transcriptomics, proteomics, metabolomics and microscopy. Our biggest challenge has been to connect all these techniques and try to get a real quantitative understanding of the system. Integrative biology is the way to move forward to achieve this goal. Integrative Biology may also be fostered through concerted efforts at the level of young scientist recruitment and training. We strive for all Master students, PhD students and postdoctoral fellows to receive some interdisciplinary training, spanning from biophysics and molecular biology to bioinformatics and mathematical modelling, before leaving the institute. Young scientists should not just specialize in one field but also develop the ability to work on multiple projects and in various fields. To summarize, our first aim is to ensure that we host diverse groups and, as an institute, we try to integrate different technologies and approaches to get a holistic view of a problem. The second aim is to provide a broad training to young scientists, generating not only good specialists but also interdisciplinary scholars. To ensure multidisciplinarity in the biomedical research conducted within the CRG, we have decided to foster three scientific and technological areas in particular. Digital Biology will be further developed so that we can produce and integrate large biological data sets as well generate models of complex biological networks. Biomedical Research will be newly defined as the combination of our current expertise on molecular mechanisms, cellular processes and systems biology with personalized medicine. And, finally, technological platforms will be reconsidered, so that we can enable self-sustainable technological services combining data integration, “omics” technologies, high-resolution microscopy, single-cell analyses and tissue engineering. We have already been able to recruit PhD students and postdoctoral fellows from various backgrounds that fit within the above areas. In addition, at the level of group leaders, we have made good progress towards fostering digital biology, as we have already recruited several physicists working on cell biology and bioinformaticians focusing on diverse topics. However, we are still trying to attract group leaders with a medical background, so that we can soon develop a novel aspect of biomedical research, which is medical genomics. As yet, we lack groups with a chemistry background. In general, recruiting groups from diverse backgrounds has not proven to be an easy task so far, due to the difficulty of finding scientists that bridge different disciplines. Fostering crosstalk among our core facilities is also a big challenge. We would like to mainly focus on cell organization, differentiation, reprogramming, or transformation, not just in the classical sense, but also involving the latest technologies available. Moreover, we would like to recruit PIs working on the human microbiome and its interactions with the host. Molecular circuits involved in organ formation are also a major area of research within the CRG. The development of new methods is our fourth priority. We cover all possible technological directions with our existing core facilities, which include genomics; transcriptomics; proteomics; protein expression amplification; generation of induced pluripotent stem cells; organoid formation; histopathology; and bioinformatics. The general aim is that any group that joins the CRG has access to training and support in all the above-mentioned fields by a dedicated core facility. Moreover, in the near future, we are planning to create incentives to foster collaborations among all our core facilities. The majority of CRG scientists come from Europe, although we also have some people from the US as well as other countries of the world. The last call for group leaders was very successful. We had excellent candidates coming from high-ranking scientific institutes worldwide. Importantly, more than half of the top candidates were women. In principle, what attracts international researchers to our institute is its reputation, the fact that core funding is secured, allowing for freedom to perform their research as independently as possible. All newly arriving groups receive a basic budget for consumables and equipment as well as guidance, leadership training and outstanding help from our administration and support services, including the Grant Support Office, so that they can apply for ERC grants and other EU funding or national grants. There have been several great achievements by CRG scientists, and it is difficult to pick just a few. For example, Bill Keyes, who is now a team leader in IGBMC, Strasbourg, but had been working at the CRG for 9 years, has produced excellent work on the role of senescence not only in ageing but also in development [1]. In addition, Roderic Guigó, coordinator of the CRG Bioinformatics and Genomics Programme, has participated in several projects and consortia, such as the Human Genome Project, ENCODE, and more recently, he has been involved in the Human Cell Atlas. A recent paper by CRG researchers revealed the 3D DNA structure of a genome-reduced bacterium showing that DNA is organized in all branches of life [2]. Research by Pia Cosma and her colleagues on the regeneration of mouse retina has been a milestone [[3],[4]]. Finally, Ben Lehner's work on the impact of environmental factors on phenotypes in C. elegans has become a classic in the field [5]. These are just examples of the excellent work done at the institute. The CRG created EU-LIFE, an association of 13 European research institutes in life sciences. The mission of EU-LIFE is to have a voice in European science policy, to exchange good practice in research management and foster collaborations. EU-LIFE has been active for more than 5 years creating strong links among its members. It defends the interests of research institutes in Europe and enables the sharing of good practice in administration, core facilities, communication, training, group leader recruitment and evaluation. In addition, it organizes yearly scientific symposia to foster scientific collaborations. A positive outcome of this initiative is the fostering of collaborations among the 13 EU-LIFE-affiliated institutes on gender equality and open science by attracting European Funding. EU-LIFE is now part of the ERA (European Research Area) stakeholder platform as well as the European Open Science Policy Platform. Today, research institutes can influence European science policy together with other actors, including universities and industry. The CRG has also created another association, which is called ‘Core for Life’ and involves European institutes that run core facilities open to the public, such as EMBL, VIB, Vienna Biocenter, Max Planck Institute of Molecular Cell Biology and Genetics, Functional Genomics Centre Zurich (FGCZ) and the Curie Research Institute. In addition, since several years, the CRG has fostered other international collaborations with top-ranking institutes worldwide, including Academia Sinica in Taiwan, the RIKEN institute on Developmental Biology in Japan, the University of Buenos Aires in Argentina and the Tel Aviv University in Israel. In our strategy plan, we also aim to support capacities development in emerging economies. To highlight is the mobility programme we developed in collaboration with Novartis to host 3–4 young researchers from Africa every year for a 6-month research-intensive internship. The main feature of this programme is that African scientists work on their own projects while hosted in CRG laboratories have access to expertise, CRG training programme and top-notch core facilities. Several of our African interns have continued their research career in Africa, obtaining jobs in companies or Universities and translating the acquired knowledge to their colleagues. Since last year, we are collaborating with the Foundation “Mujeres por Africa” (Women for Africa): every year we host an outstanding senior woman researcher, allowing her to develop her research project in our institute and boost her leadership skills. Securing functional funding for the whole institute is a challenge considering the high competition for H2020 funding. The individual groups have obtained good funding for their work but, based on the way that Horizon 2020 has been structured and is further evolving, it appears that this programme is quite applied and very much medically oriented. Thus, securing funding via Horizon 2020 might be an issue for an institute performing excellent basic research. Nevertheless, we have been successful in attracting ERC grants as well as funding from other programmes, including MCSA, FET and Infrastructure. We also have a very good track record of European-coordinated projects thanks to dedicated support that we provide to all our group leaders. Although we have been very successful in ERC calls, it is very competitive. There is a factor of luck, as there are too many good candidates applying for ERC grants. Currently, I can see no problem, but there might be an issue within the next 10 years. Within Spain, I cannot see a very bright future for research unless the state decides to increase the budget for research. There are a few institutes in Spain that receive a very good level of funding through the Severo Ochoa Programme, but research and development in one country cannot be maintained by just a handful of institutes. University research departments and small research institutes are also doing excellent research and are in need of support. Following the last years of financial crisis, there have been cuts in national funds across Europe. More money should be invested on innovation and research at the national level. There has been a tendency for EU member governments to encourage applications for ERC and other European funding, in order to make national funding dispensable. However, this is bad practice. The mission of the EU is not to replace national funding for research and technology, but to complement the existing competent national funding programmes. Therefore, I hope that national funding will be increased and some bureaucratic rules will change. In Europe, ERC has been the most successful European funding programme for many years; it is changing the way we are doing science in Europe. Today scientists can get significant funding to pursue their scientific projects with little constraints. Moreover, we have established a system that evaluates and supports science across Europe in an objective way. However, I can see the need for increasing the ERC budget by at least twofold. More ERC grants are needed, as at the moment, there are many excellent proposals that receive no funding. Another concern regarding the future of basic research in Europe is that European Framework programmes need to be more open and inclusive and not focus merely on applied projects. Firstly, in biological research, it is impossible to achieve outcomes that go to the market within a 5-year timeline. In addition, you never know where the economic success is going to come from. However, the last few calls have mainly focused on clinical trials. Human health can remain the focus of such calls, but funding agencies need to keep in mind that basic research is also closely related to human health. Funding only the last stages of drug development makes no sense.