Sabrina Sabatini

Rosie Redfield

BiotecVisions 2012, April

Lu and Dr Ronald DePinho led to the identification of prostate cancer-driver genes using high-throughput functional genomics.

The European Science Foundation (ESF)–European Molecular Biology Organization (EMBO) Symposium on Antiviral Applications of RNA Interference took place between 5 and 10 April 2008, in Sant Feliu de Guixols, Spain, and was organized by J. Kurreck and B. Berkhout. ![][1] Small RNAs are important regulators of gene expression that operate through a range of RNA‐silencing mechanisms. Of these, RNA interference (RNAi)—gene silencing through small‐interfering RNAs (siRNAs) derived from exogenous double‐stranded RNA (dsRNA)—and the microRNA (miRNA) pathway—gene silencing guided by small RNAs encoded in the genome—are the best known. The discovery that dsRNA induces RNAi (Fire et al , 1998) and the appreciation of its antiviral activity revolutionized our view of viruses in many ways. The European Science Foundation (ESF)–European Molecular Biology Organization (EMBO) Symposium on Antiviral Applications of RNA Interference brought together about 50 scientists working at the interface between virology and RNAi. Here, I review the main issues that were discussed at the meeting. RNAi provides an antiviral defence mechanism in plants, nematodes and insects. The cleavage of viral dsRNA by the ribonuclease Dicer generates viral siRNAs (v‐siRNAs), which are incorporated into the RNA‐induced silencing complex (RISC) and direct RISC activity onto messenger RNAs (mRNAs) in a sequence‐specific manner. Recognition of a complementary sequence then triggers the endonucleic cleavage (slicer activity) or translational inhibition of the viral target RNAs by an Argonaute family member (Fig 1). Figure 1. RNA silencing in virus infections. ( A ) RNA interference (RNAi) as an antiviral defence mechanism. Viruses might produce double‐stranded RNAs (dsRNAs) that are processed by the RNAi machinery and thereby programme the RNA‐induced silencing complex (RISC) to degrade viral RNAs. ( B ) Cellular or viral microRNAs (miRNAs), or viral RNAs with structural similarity to pre‐miRNAs, regulate viral and host gene expression, and contribute to viral pathogenesis. miRISC, microRNA‐induced silencing complex; pre‐miRNA, precursor miRNA; pri‐miRNA, primary miRNA … [1]: /embed/graphic-1.gif

Deep in the German forests above Heidelberg, the European Molecular Biology Laboratory (EMBL), in its infancy in the late 1970s, was a haven of basic research and serenity. I remember hard experimental work, intensive discussions and unexpected ideas emerging along the wooded paths. On a recent visit, I saw that the busy buzzing of EMBL has by no means receded. But I also saw that EMBL is changing. The explosive growth of the parking lots and the new buildings for commercial companies are reshaping the glade; scientists are sitting behind their computer screens most of the time; there are more females than males; last summer, the temperature broke another record high. And, probably much more important, the scientists working there are becoming aware that there is a world outside the laboratories. It started with rumours rising from the valley that first reminded us that a wider world was bubbling not far away. We were amazed at the gossip reported in the local press that clover, growing around the Laboratory, had a suspicious number of leaves because of some mysterious genetic manipulations. We were shocked when the media widely covered the claim made by an East German scientist that AIDS was a product of the US Secret Services. Nowadays, news about cloning, stem‐cell research, bioterrorism and the turbulence of the stock market is pouring in daily. Biologists know about change. For more than 3 billion years, life has undergone changes, and no one would be here to witness anything if evolution had not been hard at work. But the changes that are now occurring are different, because they are anthropogenic and because they are happening increasingly rapidly. And they are not met with enthusiasm by everyone: “Stop improving things!”, an angry hand had written on the door of the computer room. …

Editorial26 March 2009Open Access EMBO Molecular Medicine: Conquering new frontiers Matthias W. Hentze Matthias W. Hentze [email protected] European Molecular Biology Laboratory Directors' Research, Heidelberg, Germany Matthias Hentze is a Senior Editor of the Journal and is at the European Molecular Biology Laboratory. Search for more papers by this author Matthias W. Hentze Matthias W. Hentze [email protected] European Molecular Biology Laboratory Directors' Research, Heidelberg, Germany Matthias Hentze is a Senior Editor of the Journal and is at the European Molecular Biology Laboratory. Search for more papers by this author Author Information Matthias W. Hentze1 1European Molecular Biology Laboratory Directors' Research, Heidelberg, Germany EMBO Mol Med (2009)1:5-5https://doi.org/10.1002/emmm.200900011 PDFDownload PDF of article text and main figures. ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions Figures & Info Dear colleagues, I am excited by the launch of EMBO Molecular Medicine, which marks a new era in the activities of the European Molecular Biology Organization (EMBO). The Journal offers a new vehicle for exploration of one of the most promising frontiers in the life sciences. At the same time, for me personally, it also completes a circle with regard to my scientific interests. After training in the 1980s as a medical doctor (with the aim of becoming a hepatologist), I became—at a time when medicine was still more an ‘empirical art’ than a hard science—more and more fascinated by the power of molecular biology. My fascination took me deeply into mechanistic molecular aspects of (post-transcriptional) gene regulation, and considerably further away from medicine than I had anticipated. However, with a growing appreciation of the potential of ‘Molecular Medicine’, I benefited from astute observations made in ‘the clinic’ that gave rise to new and important insights into basic mechanisms of gene regulation. β-Thalassaemia and nonsense-mediated (mRNA) decay as well as thrombophilia and altered mRNA 3′-end processing are personal examples of discoveries that emerged from ‘the clinic’ rather than from the study of model systems. »The journal offers a new vehicle for exploration of one of the most promising frontiers in the life sciences.« Conversely, the opportunities of ‘bench-to-bedside’ research are far better known, and my group actively pursues these in the context of diseases of iron metabolism such as overload and anaemias. EMBO as a basic life science organization is known for its commitment to excellence, recognition and fostering of scientific talent and last but not the least collegiality. The launch of EMBO Molecular Medicine is an open invitation to clinical scientists to become a part of the EMBO community. »The launch of EMBO Molecular Medicine is an open invitation to clinical scientists to become part of the EMBO community.« This invitation opens up a precious intellectual and collegial resource to the clinical community, but at the same time, I am absolutely convinced that the success of EMBO Molecular Medicine critically depends on the active embracement of our new Journal by clinicians. Basic researchers and clinicians alike have much to gain from sharing their complementary expertise and resources, and from developing common values. Only jointly can we conquer what is likely to be the most exciting frontier in life sciences research of coming decades. I will do everything I can to support this conquest. Come, join the EMBO Molecular Medicine community! Matthias W. Hentze Previous ArticleNext Article Volume 1Issue 11 April 2009In this issue RelatedDetailsLoading ...

Professor Michael J. Pikal: Scientist, family man, educator, colleague and friend

RNA silencing is a complex and highly conserved regulatory mechanism that is now known to be involved in such diverse processes as development, pathogen control, genome maintenance and response to environmental changes. Since its recent discovery, RNA silencing has become a fast moving key area of research in plant and animal molecular biology. Research in this field has greatly profited from recent developments in novel sequencing technologies that allow massive parallel sequencing of small RNA (sRNA) molecules, the key players of all RNA silencing phenomena. As researchers are beginning to decipher the complexity of RNA silencing, novel methodologies have to be developed to make sense of the large amounts of data that are currently being generated. In this review we present an overview of RNA silencing pathways in plants and the current challenges in analysing sRNA data, with a special focus on computational approaches.

The study of peptide hormones is a rapidly and dynamically developing field of biology throughout the world, closely associated with the latest achievements of fundamental science and medical practice. The study of peptide hormones was greatly influenced by recent major events in science. In the mid-70s, thanks to classical studies by F. Sanger et al., A. M. Mahat and W. Gilbert, efficient methods for sequencing DNA nucleotide sequences were developed. Later this event became known as the revolution in molecular biology. Together with the existing methods for cloning fragments of nucleotide sequences in plasmids and phages, they made it possible to develop a modern recombinant DNA methodology, which formed the basis of rapidly developing genetic engineering biotechnology, bioorganic chemistry, molecular genetics, microbiology, virology, and a number of other scientific disciplines. Recent advances in molecular biology have tremendously accelerated the entire process of scientific knowledge and made it a reality, for example, to develop global scientific programs such as the study of the complete nucleotide sequence of the human genome. It is no exaggeration to say that over the past 20 years, biological science has accumulated more experimental data than over the entire previous period of its development. At present, 70-80% of research in the advanced countries of the world is carried out using molecular biology methods, which now allow us to solve such scientific problems within 1 year that previously had to be spent decades.

Pathology remains as one of the most important medical specialties, playing a pivotal role in diagnosis as well as in elucidating the pathogenesis of several diseases. Pathologists usually build a bridge between basic sciences and clinical practice, and are important players in translational biomedical research. Considering the foregoing information, it is clear that pathology is an important piece in medical education, since it provides a unique learning platform that unites molecular, cellular, mechanistic and structural alterations of human diseases. However, despite the multiple possibilities offered by the practice of pathology, Brazil is getting short of pathologists, mostly those interested in academic and investigative pathology. This situation has a trend to worsen, since the number of medical schools in Brazil increased significantly in the last few years. In such a context, it is almost mandatory to devise strategies to increase the efficiency of diagnostic pathology and to attract medical students to the specialty. The causes of the process that made pathology not so attractive to medical students have not been hitherto clarified. Potential agents are the monetary revenue of pathology practice, the emergence of new diagnostic areas, such as molecular biology and radiology, and, possibly, the context in which pathology is taught in medical courses. Indeed, it is quite possible that the courses of pathology are not clearly depicting the possibilities of professional and scientific achievements that pathology offers. At Faculdade de Medicina da Universidade de Sao Paulo (FMUSP), we decide to face the challenge, by including pathology throughout the six years of medical course. In the first two years, we used autopsies as the basis for education. The idea is to take advantage of a large autopsy service that performs about 15,000 autopsies of non-violent deaths per year. In this service, we installed a state-of-the-art imaging system that includes a 16-channel CT scanner, an ultrasound scanner, a 7-tesla magnetic resonance imaging (7T MRI) machine, 3-D printers, as well as a digital slide scanner. With such a platform, designed for research and teaching, we developed procedures capable of performing post-mortem angiography and spectroscopic metabolomics. In those activities, young medical students are exposed to a clinical discussion, the in-vivo and post-mortem images, followed by the autopsy, which is transmitted in real time from an autopsy room equipped with image facilities. The activity occupies an entire four-hour period and has the presence of basic scientists, clinical and anatomic pathologists, general clinicians and radiologists. More recently, we added professors of medical humanities, since the autopsy table is one of the settings where inequalities of access to medical treatment, driven by social and economic factors, are clearly observed. These activities are conducted on a weekly basis during the first two years of medical school and are highly appreciated by students. In the following week, they are exposed to histological preparations of tissue samples collected during the autopsy procedure. Since there are not many pathology services with the conditions to develop such a type of instruction, we explored the possibility of expanding our classes to other institutions. Indeed, once a month, we have the pleasure of sharing our classes with other medical schools by telepathology, and we have received a lot of inputs from students, clinicians and pathologists from the other schools, reducing our cultural inbreeding and expanding our experience. The autopsy-based learning began in 2002 and evolved until reaching the present form. Although the experience has not been so long, it is possible to identify two important impacts. First, the number of medical students from our institution applying to residence in pathology increased. Second, the autopsy course was ranked among the three disciplines that contributed most to medical education, as expressed by students at the end of the course. Apparently, expressing clearly the potential of pathology during the medical course is one of the strategies that may augment the number of pathologists in our country, and contribute to improve medical education. Thus, it is time to interact and use telepathology to build a network of medical schools, in order to face the challenge of teaching pathology in a scenario where the number of medical schools is increasing. By doing this, medical students will appreciate the beauty of our specialty and more and better pathologists will be graduated in our country.

Lysosomal Storage Disease Factors: the Work of Elizabeth F. Neufeld

Stanley J. Korsmeyer

Karan ("Josh") Abraham is a physician-scientist trainee in the University of Toronto MD-PhD program. He is a Vanier Scholar, Ruggle's Innovation Award winner, Adel S. Sedra Distinguished Graduate Award recipient, and is currently president of the Clinician-Investigator Trainee Association of Canada (CITAC). In his PhD work, he uses molecular, genetic and cell biological approaches to uncover mechanisms that preserve the integrity of the genetic code and sustain the protein synthesis capacity of cells. He hopes to lead a basic research program that will advance scientific knowledge to better understand and treat human disease, and to one day become a leading ambassador for Canadian biomedical research.

The EMBO Journal is run by the European Molecular Biology Organization, EMBO: an organization run by scientists, for scientists. EMBO aims to promote excellence in science, transparency, efficiency and inclusiveness. These are also cornerstones of The EMBO Journal . In this light, and in response to discussions in the community, we are introducing three major changes in The EMBO Journal from 1 January 2009: The editorial process often appears to be a black box, despite it being an integral part of science. When things work well, referee–author–editor interactions can be very constructive. But they can also be endlessly frustrating. These issues have been discussed in recent commentaries from the scientific community. One may ask: is the editorial process at a journal efficient and reasonable? Are referees rightfully critical or too picky and too demanding? Do editors make reasoned decisions and minimize unnecessary back‐and‐forth cycles? We believe The EMBO Journal has an efficient and reasonable editorial process. Instead of just saying so, we will make it visible. A transparent editorial process will help demystify decisions. A separate, and equally important, aspect is that a transparent process should encourage constructive referee and author argumentation. This new initiative is described in detail below. With ever increasing number of reviews and limits on article length, it is tempting to cite reviews even when the primary literature is still recent. This is unfair to authors of the original papers. To counteract this, we strongly encourage authors to cite primary literature whenever possible. At The EMBO Journal , we will actively back up this encouragement by completely excluding the references from the character limit and from any page charges. So authors can now freely cite all the papers they need to cite. Although increasing the citation of the primary literature is our main objective here, we …

Interview by Jenaid Rees, Commissioning EditorRino Rappuoli is the Global Head of Vaccines Research at Novartis Vaccines & Diagnostics (Siena, Italy). Previously, he was Head of R&D (Sclavo, Italy), and then Head of Vaccine Research and Chief Scientific Officer at Chiron Corporation (CA, USA). Rappuoli earned his PhD in Biological Sciences at the University of Siena (Siena, Italy) and has served as visiting scientist at Rockefeller University (NY, USA) and Harvard Medical School (Boston, MA, USA). His team developed the first recombinant bacterial vaccine (against pertussis) and the first conjugate vaccine against meningococcus C and A. He also worked on the MF59 adjuvant used in a vaccine against pandemic influenza and an experimental vaccine against Helicobacter pylori. Rappuoli and his team pioneered the genomic approach to vaccine development termed reverse vaccinology and used it to develop a vaccine against group B meningococcus. Among his scientific contributions, he was cofounder of the field of cellular microbiology, a discipline that has merged cell biology and microbiology. He is a member of numerous international associations, including the US National Academy of Sciences, the American Society for Microbiology and the European Molecular Biology Organization and serves on the Expert Review of Vaccines Editorial Board. He is also a recipient of several prestigious awards, including the Paul Ehrlich and Ludwig Darmstaedter Prize.