From Science Fiction to Science Fact
12th International EMBL PhD Student Symposium

21-23 October 2010
Heidelberg, Germany

Organisers:

Draft Report

Summary

The 12th International EMBL PhD Symposium was held in the Advanced Training Centre, Heidelberg, from the 21st to the 23rd October, 2010. Around 120 participants convened each day to discuss the cutting edge of different fields of science during the four sessions of the symposium. In the first session, dedicated to cell and structural biology, physical properties of cells were presented along with high-­-throughput proteomics and advanced spectroscopy techniques. The second session covered medical topics both at DNA and protein level, but also with a strong focus on more system-­-wide approaches, as presented by dr. Panos Deloukas and dr. Rudi Balling. Different omics, from gene regulation to proteomics and metagenomics, were the subject of the third session. The symposium concluded with a “science that looks like fiction” session, where extremely robust life forms and behaviour control caught audience’s attention. The talks by invited speakers were interweaved by chances for the participants to mingle and share ideas: many of them presented their research in short talks during the three days, while others had the opportunity to do so during the two poster sessions. Moreover, a panel discussion allowed the audience to discuss the relationship of science and fiction, not only with other scientists but also with people who work at the interface between science and society. Encouraged by the positive experiences from this meeting, the next International EMBL PhD Symposium will take place in November 2011.

Scientific Content

Day one: Structural and cell biology Thursday 21st October
Session overview:
Antonio Siccardi (Università Vita Salute San Raffaele, Milano): "Archeology of a paradigm"Jochen Guck (University of Cambridge): "Do biological cells care about physics?"
Rudi Balling (LCSB Luxembourg): “The LCSB in Luxembourg: From Systems Biology to Systems Biomedicine”
Qihua Ling (University of Leicester): "Genetic analysis of the protein import machinery of Arabidopsis plastids"
Angus Lamond (University of Dundee) (EMBO Lecture): “Super Experiments and Application of System-wide Proteomic Analyses in Cell Biology”

Session description:
The Opening lecture set the stage, from the historical point of view, for scientific discussion on how scientific paradigms develop and evolve. The main session of the first day focused on the state-of-the-art technologies and new discoveries in the fields of structural and cell biology.

Opening lecture: The Symposium was opened by a lecture on history of science. Professor Siccardi recounted the audience about the fascinating scientific journey of Jacques Monod from the 1940s to the 1960s that led from studies on bacterial diauxic shift to the formulation of the operon model of gene regulation. The talk was sustained by the explanation of the key experiments that led Monod and coworkers to steer and shape the model up to the paradigm that laid the grounds to modern molecular biology, showing a clear example of the proceedings of scientific thought. The lecture provided the perfect framework to discuss about future developments of science and to critically discuss the following talks.

Session I: Structural and cell biology

As the first speaker of our structural and cell biology session, the physicist Jochen Guck introduced the mechanisms of cell deformation probed by an optical stretcher. He pointed out how, by investigating the cell compliance to stretching, cancer cells can be differentiated from healthy cells and how he can even specifically determine if cancerous cells are in a metastatic state, therefore providing a potential new readout for cell phenotypes. In addition, he gave insight into the light conducting properties of retinal Müller cells and into how these kinds of properties can be read out with the help of laser physics.

Qihua Ling, the second speaker of the structural and cell biology session, introduced the new findings on the composition and specificity of the TIC and TOC complexes of Arabidopsis chloroplasts. These protein complexes are responsible for protein transport into plastids and span the inner and outer plastid membrane. Qihua Ling focused specifically on a genetic analysis of different TIC and TOC components, their different isoforms and their implications for transport specificity.

Angus Lamond held the last lecture on the first day and presented new mass spectrometry techniques that not only identify proteins within the proteome but also connect protein localization with protein turnover by pulse-labeling experiments. He introduced furthermore the idea of stable isotope labeling in order to quantitatively compare and analyze protein compositions under different biologically relevant conditions. Dr. Lamond also presented database tools for the analysis of multidimensional proteomics data.

The first talk of the Medical research session was given on Thursday by Prof. Rudi Balling. He introduced his perspective on the emerging change in medical research from a molecule centred dogma to a more systemic view Prof. Balling envisioned closing the circle from medical observations, made on a single molecule level, to an integrated system level perspective with the help of increased understanding of molecular networks. He exemplified this on the process of inflammation, a process that is a close part of many diseases of high clinical relevance, such as neuro-degenerative diseases, diabetes and cardio-vascular diseases.

Day two: Medical research and Panel Friday 22nd October
Session overview:
Fabrizio d'Adda di Fagagna (IFOM Milano): "Cellular senescence in cancer and ageing"
Tamas Fischer (University of Heidelberg): "Epigenetic control of cryptic transcription and genomic stability"
Christian Haass (LMU Munchen): "The Molecular Clockwork of Alzheimer's Disease"
Peter Hildebrand t (TU Berlin): "Raman and IR spectroscopic approaches for studying protein structure and dynamics"
Panos Deloukas (Sanger Institute Hinxton): "Genetics of coronary artery disease"
Panel talk by Alastair Reynolds: "Myths of the Martian future"
Panel discussion with Giovanni Boniol, Panos Deloukas, Armand Leroi, Alastair Reynolds, Jon Turney: "The interplay between Science and Science Fiction"

Session description:
The 2nd session of the symposium set-out to deal with the medical implication of basic research, especially in the light of the new technological possibilities of the various omics techniques. The session had been primed by Prof. Ballings talk on the day before.

The first talk of the second day was given by Dr. Fabrizio d'Adda di Fagagna, who demonstrated the importance of DNA damage repair in cellular senescence and cancer. He presented evidence that telomeric DNA resists DNA repair, and that irreparable DNA damage occurring at the telomeres plays a role in cellular senescence. Furthermore, Dr. d'Adda di Fagagna showed ex c iting and unpublished results demonstrating the role of (non-coding) RNA for DNA damage response. These results may have important implication in medicine as they open up a new way of interfering with this important mechanism.

The second talk of the day was given by Dr. Tamas Fischer from the University of Heidelberg. He highlighted the importance of non-protein-coding RNAs in the epigenetic regulation of transcription. Dr. Fischer discussed how non-coding RNAs can control genomic stability, loss of which is a major cause of cancer development.

Professor Haass traced in his talk a concise, but clear and exhaustive history of the main discoveries that have led to the current understanding of Alzheimer's disease (AD) pathophysiology. He highlighted the difficulties in trying to treat this dementia, pointing to the future possible paths and hinting to the possible benefits that could come from pharmacological studies in familial AD carriers. T he talk mixed to solid science also ethical and social issues.

Bridging the Medical and the Omics was the following talk of Dr. Panos Deloukas. He introduced the audience to genome-wide association studies, in particular to the work done in order to identify loci implicated in the risk and development of coronary artery disease (CAD). Dr. Deloukas discussed the benefits of knowing the genetic determinants of complex traits, together with the known challenges of identifying them . He presented the results and prospects of the CARDIOGRAM programme, a large collaborative project involving 130,000 individuals genotyped for CAD determinants. In this project, 25 CAD risk loci were identified, some of which have also been verified with expression quantitative trait loci (eQTL) mapping.

As a continuation from the first day, Peter Hildebrandt presented how infrared and Raman spectroscopy could help to understand complex enzymatic reactions and enzyme/cofactor interactions. He mainly focused on the well known cytochrome c and its structure changes in dependence on electric fields, which is of high relevance in order to get better insight into how electron transport within the respiratory chain is mediated on a structural, dynamical and conformational level. He explained also new achievements in the area of surface enhanced Raman and IR spectroscopy that were used in the studies he presented.

Panel talk

The panel talk was given by Dr. Alastair Reynolds, who presented a very interesting overview of how space science-fiction has changed in reaction to new scientific knowledge. His “case study” was Mars, and the different novels that take place in Mars or in Mars-like worlds. H e then generalised his views to all of science-fiction and gave his own experience of new science contradicting one of his previously published science fiction books.

Panel

The panel discussion was lively and insightful. The conversation flowed naturally, and questions and comments from the audience made the conversation go naturally to the topics that were intended for discussion. Dr. Boniolo and Dr. Deloukas in particular were wary of heightened expectations in the field of biomedicine that science fiction might create, the former panellist due to his background as a medical doctor and bioethicist, the latter drawing from his work in human genetic markers and his interactions with the media. Prof. Leroi, Dr. Reynolds and Jon Turney countered, each from different backgrounds. In their opinion the excitement that science fiction creates has more positive than negative effects.

Responding to the audience's comments, the second part of the panel focused on the pessimism or optimism about the future as depicted in science-fiction over time and how this relates to how science is perceived.

Day three: Omics and Science fiction Saturday 23rd October
Session overview:
Omics
Len Pennacchio (JGI, California): "Large-Scale Identification of Tissue-Specific Enhancers In Vivo"
Ruedi Aebersold (ETH Zurich): "Mapping and Measuring Proteomes"
Jeroen Raes (Vrije Universiteit Brussel): "You are not human: investigating the human microbiome"

Science Fiction
Miroslav Radman (Université Paris 5): "The biology of robust species"
Gero Miesenboeck (University of Oxford): “Lighting up the Brain”

Closing speech: Jon Turney (Bristol, UK): "The history of biological futures"

Session description (Omics):
The third session was devoted to high-throughput technologies, many of which had already been touched upon during earlier sessions of the Symposium. In particular, the focus was on gene regulation, proteomics, and metagenomics.

Dr. Len Pennacchio discussed challenges in decoding the human non-coding genome and the work in his laboratory geared to elucidate the genetic “enhancer code”. He highlighted the importance of the non-coding genome in human medicine by mentioning that 40% of disease-associated SNPs are not linked to any coding gene. Dr. Pennacchio' lab has focused on screening of tissue-specific enhancers important for tissue development using sequence conservation and ChIP-seq. They used these technologies to find 17,000 in vivo binding sites of p300 in eight embryonic mouse tissues, and the accuracy o f the approach was shown further in transgenic mice. These data add another layer of functional annotation to the non-coding human genome, important for the understanding of human biology and disease.

The second invited speaker of the day, Dr. Ruedi Aebersold, discussed the goals for new proteomics technologies. A current focus of his research is in the generation of complete mass spectrometric proteome reference maps that could be used in a similar manner as genome references today. Fiction still today, Dr. Aebersold outlined the steps that need to be taken to transform these maps into solid facts, and the many challenges associated. He presented state-of-the art technologies for synthesis of complete mass spectromentry readable yeast proteome. Touching upon medical aspects, Dr. Aebersold also discussed how close or far we are from using proteome measurements from blood as diagnostic tools.

Dr. Jeroen Raes presented exciting findings regarding the microbial, mostly commensal, communities inhabiting the human body. The human body is a habitat for a diverse community of microbial species, and the total number of these cells outnumbers that of human cells. Medically relevant as linked to many disease phenotypes such as obesity and immune response development, Dr. Raes discussed the impact of age, gender, body mass index, and other factors on the diversity of the microbiome. He also contemplated on the cause-consequence relationship between the human (gut) microbial communities and disease states, and how the current techniques could also be used in detection of diagnostic markers for flora-related diseases.

Session description (Science fiction):
The main goal of the science fiction session was to increase the awareness of research areas that are poorly understood by the general public and in most scientific communities. These areas are often perceived as science fiction even though findings in these areas are science fact. We encouraged the speakers to propose their vision of the future in their research area. Two scientists spoke during this session: Miroslav Radman and Gero Miesenböck.

Miroslav Radman emphasized that learning from robust species might enable us to trick aging. These species all have very effective methods to protect their proteome and genome, some of which could be transferred to medical applications in the future. These include agents that can protect one's proteome from oxidation, which at some point in the future might lead to a life prolonging medicine.

Gero Miesenböck embraced the possibility to speak about a science fiction theme not only comparing himself to the science fiction figure “Dr. Gero”, but also amusing the audience with a short clip from “The Jay Leno Show” about optogenetics, a methodology developed by Miesenböck and others. He showed some of the new possibilities researchers have when designing their experiments using this methodology. It seems that optogenetics will lead to a number of new discoveries within the next years. Being able to manipulate specific neuronal patterns will allow scientists to pinpoint the function of single clusters of neurons, thus allowing the drawing of more precise functional neuronal networks.

Closing speech
The closing address was given by Jon Turney. He gave an overview of how science fiction – and public opinion in general –perceived science in the past century. In this travel through time, he crossed hopes and fears science elicited in the western society, and he implicitly prompted the audience to shape and communicate their research in positive light.

Presentations by participants: Short talks and poster sessions
One of the major goals of EMBL international PhD student symposia is to give students the opportunity to present their research. In between the detailed scientific presentations of invited speakers, our sessions were completed by compact, 20 minute short talks held by eleven selected participants.

The wide range of scientific backgrounds of the symposium's participants led to a broad and strongly interdisciplinary collection of topics. Fluorescence properties of nanocrystals and the role of early serotonin were discussed, as well as embryogenesis of barley pollen, novel approaches for diabetes treatment, and genetic variations in strains of Darjeeling tea.

Another opportunity to present their work was given to the participants through the two scheduled poster sessions. This year fewer posters than expected were presented. However, different topics were covered, from the regulation of BACE1, a key molecule in Alzheimer 's disease, to current approaches in drug discovery.

Writing Prize: “From science fiction to science fact – or vice versa”
The prize is given annually to PhD students producing outstanding pieces of science writing that communicate topical issues in a creative way to non-scientists. This year's participants were encouraged to write an essay addressing a common scientific misconception, relevance of one's research to the general public, or the relationship between science and fiction.

This year the prize was awarded to essays “A Future History Lesson in Synthetic Biology” by Sean Cheng (University of Cambridge, UK) and “Getting to the roots” by Francesca Moretti (EMBL, Germany).

Assessment of the results & impact of the event on the future direction of the field
Having set the framework with the historical and methodological Opening address, the talks flowed naturally one after the other, stitching together the four sessions of the symposium. The grounds laid by the Structural and Cell Biology session served as foundation to build the discussion of the Medical session, which in turn gave rise to questions addressed in the Omics session, prelude to the inspiring Science Fiction talks.

The programme provided the young crowd with plenty to think about, and discussion overflowed from the plenary session to the exhibition hall and beyond. It was also a great chance for PhD students to get in touch with scientists at the cutting-edge of their fields and to catch a glimpse of science that may seem fiction today but might just become established knowledge tomorrow.

Although the overall topic of our symposium attracted participants from various fields of research and therefore yielded in a highly inhomogeneous auditorium, the talks were stimulating and well received by everyone. This effect could be seen especially from the high activity of the participants in asking questions after the lectures but also in their interactions with the speakers during coffee breaks and poster sessions.

The tradition of annual EMBL PhD Student symposia is to be continued next year. Entitled “The Rhythm of Life: Cycles in Biology”, the 13 th International EMBL PhD Student Symposium will take place at EMBL-Heidelberg 17 th -19th November 2011. The goal is to explore the cyclic behaviours and dynamics present at different scales of biological complexity, from metabolism and signalling to development and behaviour.