Archive | August 2012

Doing real translational research: from patient to molecule

The Myogenesis, Inflammation and Muscle Function group from IMIM-Hospital del Mar Research Institute, coordinated by Joaquim Gea, is one of the few groups where a real translational research is already taking place. Formed 15 years ago by a group of clinical doctors specialized in respiratory diseases and a group of more basic biologists, its aim is to find direct links between specific symptoms and cellular and molecular mechanisms. For this, they do a clinical evaluation of the patient (or the animal model), obtain biological samples and do physiological studies. This part is done at the human physiology laboratory at the Hospital del Mar (or at the PRBB animal facility if it is an animal model). Then, at the respiratory biology lab at IMIM, the cellular and molecular analysis of the samples takes place.

Research at the unit is aimed at the diagnostic and treatment of respiratory diseases such as lung cancer, the cause of 20% of all cancer deaths. They also study chronic obstructive pulmonary disease (COPD), a disease caused by smoking which is more and more frequent (9% of the adult population, or 14% in men only). Sepsis (an extended blood infection), the most frequent cause of death at intensive care units, which causes exaggerated inflammatory mechanisms all through the body, is another of the diseases studied here. The group has also small projects in other non-respiratory disease, such as adolescent scoliosis (an anomalous rotation of the spinal cord) and fibromialgy, a disease which causes strong pains and tiredness and which affects 2-5% of the adult population, especially women.

The group is internationally-recognized and the most outstanding Spanish laboratory in the respiratory muscles field. It is divided into three research lines which cover different pathological mechanisms of their diseases of interest: local inflammation as a signal mechanism, a line directed by Joaquim Gea; structural and immunological alteration of the muscles and the respiratory tracks, directed by Mauricio Orozco-Levi; and local and systemic oxidative stress, directed by Esther Barreiro, the only one who is exclusively involved with research and is, for the moment, not doing any clinical activity. The three of them combine research with teaching at the UPF.

According to Gea, the biggest challenge in this field is to find drugs for the specific targets that are being identified. Interestingly, the mechanisms of loss of muscular function are very similar for the different diseases, so some of the common symptoms could have similar therapeutic approaches.

Apart from their own studies, the unit also acts as a reference laboratory, designing studies for other groups and analyzing samples from different regions in Spain, the UK, The Netherlands and Canada. The unit also collaborates with other groups at the PRBB, such as that of Pura Muñoz (CEXS-UPF) and that of Josep M. Antó (CREALIMIM).

This article was published in the El·lipse publication of the PRBB.

Several open positions at CRG with upcoming deadlines

The CRG has published several scientific job openings on their homepage:

They are currently seeking up to five people to set up the CRG-EBI operation, a joint program with the European Bioinformatics Institute (www.ebi.ac.uk) to explore and develop joint services based around human sequences and genotypes, in particular those associated with phenotype information. The openings are for a Team Leader, a Senior IT Technician and three IT support-staff. Please check the job offer.

Additional offers are for a Computational Scientist at the CRG/UPF Proteomics Unit in Barcelona, one postdoctoral position at the laboratory of Dr. Salvador Aznar Benitah, group leader of Epithelial Homeostasis and Cancer, within the programme of Gene Regulation, Stem Cells and Cancer,  and a Bioinformatician position at the laboratory of Dr. Luis Serrano, group leader of Design of Biological Systems, within the programme of Systems Biology.

The look of the retina

The retina, or photosensitive layer, forms the deepest layer of the posterior compartment of the eye. It consists of three basic types of cells: neurones, pigmented epithelial cells and neuronal support cells. Different photoreceptor cells can be distinguished among the neurones: the colour receptive cone cells and black and white receptive rod cells. A third type of photoreceptor cells has photosensitive ganglions, responsive to light intensity. The CMRB is working on different protocols to differentiate retinal cells from stem cells, with the aim of future application in regenerative therapy. The picture shows a cell culture in the process of differentiation to retinal from stem cells, positive for the neuronal markers Pax6 in green and Tuj1 in red.

“Our translational research makes us compulsive collaborators”

The Molecular physiology and channelopaties research group from the CEXS-UPF is formed by several PhD students, postdocs, a technician and a couple of principal researchers with teaching duties. Miguel Angel Valverde leads the group since 1999, when he came to Barcelona from King’s College in London.

The aim of the group is two-fold. On the one hand, they try to understand how the ionic channels are activated, how they sense the physical or chemical signals that tell them to open or close. The second goal is to understand what happens when these channels don’t work correctly.

Ca2+ and its role in disease

Different types of ion channels are present in all cells, but they all have a unique, essential function: to modify the electric potential of the cell with the ultimate goal of regulating the intracellular Ca2+ concentration. Indeed, Ca2+ is not only an ion itself, but also a signalling molecule involved in many processes, such as muscle contraction, neurotransmitter release, or even gene transcription. This is why, when its concentration is deregulated, problems as diverse, common and complex as cardiovascular, respiratory or neuronal pathologies can arise. And these are precisely the channelopaties that the group studies.

Hypertension is one of the most important predictors of cardiovascular diseases. And one of the causes of hypertension is the contraction of the arteries, which makes their diameter smaller. This contraction is started by the Ca2+ signalling in the vascular smooth muscle. Ca2+ concentrations are also crucial for the immune system response, which explains why the group is interested in asthma, an inflammatory pathology. Finally, migraine is caused by a hyper excitability of the brain cortex, which in its turn is caused by an increase in the activation of synaptic transmission. Again, we find the usual suspect, an increase in Ca2+ levels, at the beginning of the chain of events that lead to migraine.

A multidisciplinary approach 

role of ion channels in these channelopaties is studied at the genetic, molecular, cellular and physiological level. The group collects population samples, either by themselves or in collaboration with clinical or epidemiological groups. They sequence some candidate genes to find any genetic variations (called polymorphisms) that may be linked to the pathology. Once there is a polymorphism that represents a clear risk or beneficial factor, the group studies why this change in the genome is associated with the disease. “We don’t just link a gene to a disease. Instead we want to understand the whole process: how this gene affects the protein structure, and how that change in structure affects the function of the channel and the Ca2+ concentration”, explains Valverde.

They introduce the genetic changes under study in cells in culture and they analyse how the Ca2+ concentration varies by fluorescent microscopy, or do electrophysiology studies to look at the electrical activity of a single channel.
Such a multidisciplinary work requires lots of collaborations, and the laboratory has found many of them within the PRBB. They have worked with researchers at the IMIM and with neurologists and pediatricians at the Hospital del Mar for the cardiovascular and asthma studies; with groups at the CRG and other colleagues at the UPF and the GRIB for some genetic, biochemical and computer modelling aspects of the studies. “We do truly translational research, and are compulsive collaborators”, concludes Valverde with a smile.

This article was published in the El·lipse publication of the PRBB.

“I’m working at what I’d always dreamed of” – Manuel Pastor, researcher on drug design

An interview published in Ellipse, the monthly magazine of the PRBB.

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Manuel Pastor, 45 and from Madrid, studied pharmacy at the University of Alcalà de Henares (Madrid), and after doing his PhD in the organic chemistry department went to Perugia in Italy for his postdoc. Self-taught computer expert and passionate about reading and the cinema, Pastor fell in love with medicines when he was little. Years later he has realised his dream as head of the research group for computer aided drug design at the GRIB (IMIM-UPF).

When did you hear the call to science? 
I’ve been passionate about medicines since I was small. When I was 5 my brothers used to read Spiderman comics and I remember clearly that I was intrigued by the hero, a scientist, who created compounds that could reverse the effects of the bad guys’ poisons. I wondered how these compounds worked in the body. Straight away I started to say that I wanted to work in research. My friends just laughed and asked me if my parents were rich. “No? Then forget it!” I come from a humble family, but with a bit of luck and dedication I’ve turned out OK.

So you owe your vocation to Spiderman? 
I think it is a fascinating comic. Today there are so few cases where the hero is a student, an intellectual and committed person, with values.

How was your postdoc in Italy? 
It was 1994, when Internet was just starting to become known about and used. There was everything to do. When I arrived in Italy I installed the first browser on the lab computers; they hadn’t even realised that they could access information and databases via the Internet!

Are you not a pharmacist then? 
Yes, but I learnt to program during my doctorate. In fact, toward the end of my thesis I created one of the first computer networks in Spain – and when I say created I mean I physically joined the cables from one computer to another! After the postdoc in Italy I went back to Madrid for a year and a half, but it was a bad time, much worse than now, and there was no work anywhere. I went back to Perugia where I was offered a job in a scientific software company (Multivariate  Infometric Analysis). I worked there for three years as head scientist.

And finally you came back… 
It was 1999 and this time Ferran Sanz contacted me because they needed biostatistics teachers that also fit in with the research areas of the IMIM. Mostly the teaching attracted me, I’ve always liked it. For me giving classes is not secondary, it is important.

What differences have you found between the worlds of academia and industry? 
They have different objectives and methods. I think the important thing is to find out which the good things are from each and try to apply them. My group is just at the interface between these two worlds.

And what are the best bits of each world? 
From the company world I like the clear objectives and practical results. I don’t have anything against basic research, but I want to do research that impacts the world I live in. In academia there is more creative freedom and more contact with young people, researchers just starting out. This is especially enriching because having to explain things lots of times means that in the end you understand them better yourself!

The path to life of the zebrafish

The path to life of the zebrafish

This picture of the department of Histology and Bioimaging of the CRMB shows different stages of Zebrafish embryonic development using a confocal laser microscope. The actin is stained red and in blue the yolk, which feeds the developing embryo. The phases are fist one cell, then two cells, four, and finally the result 48 hours after fertilization.

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