The colours of science
The colours of science
Science, in its day-to-day form, presents itself full of colours, as many as a painter’s palette and with the rainbow’s range of tonalities. The single nucleotide polymorphisms (SNPs) are the most common variations of the human genome. These small modifications are very useful in medical research of complex diseases and to develop new drugs. The SNPs present few variations between generations, a fact that allows us to follow the evolutionary processes in studies of population genetics. They are also used in some genetic tests, such as paternity tests or forensic analyses.
The use of SNP arrays, seen in the image, allows the analysis of up to 1 million SNPs in a single reaction. This system generates an impressive amount of data from less than one microgram of DNA; an amount of data that years ago no researcher ever dreamed of having so quickly.
This image was published in Ellipse, the PRBB monthly newspaper.
Neuropharmacology Research Unit (CEXS-UPF)
Drug abuse and emotional disorders, such as anxiety and depression, are generating a serious social problem. This is why Rafael Maldonado’s neuropharmacology group at the CEXS-UPF studies the common biological mechanisms involved in these two phenomena. They focus particularly in nicotine, cannabis, cocaine and ecstasy, and in the possible mechanisms underlying the abusive consume of these substances.
Maldonado explains there are three factors to understand why some people become addictive and others don’t: drug consume (the quantity, the frequency, the mode); social and environmental factors; and individual vulnerability, which includes genetic factors. A classical example of the effect of the environment is how the American marines that were heroin addicts in Vietnam quitted easily once back at home.
In order to understand addiction and emotional disorders, the group, formed by 29 people, uses different techniques: classical pharmacological strategies, using compounds that act on the nervous system receptors; ‘knock-out’ mice in which a specific gene has been deleted in order to understand its function; and animal models for behaviour studies which, according to Maldonado, are very complex but once they are established they allow a good prediction of what can happen in humans.
Maldonado highlights the discovery that specific components of the endogenous opioid system are a common substrate for different addictive behaviours as a major contribution of his group. His dream: that this knowledge gives rise to effective treatments for the addicts, who are people with a chronic disease, emphasizes the researcher.
This article was published in the El·lipse publication of the PRBB.
“The discovery of giant viruses was revolutionary”
An interview recently published in Ellipse, the monthly magazine of the PRBB.
Jean-Michel Claverie is the director of the Institut de Microbiologie de la Méditerranée in Marseille. A physicist by training, he first encountered biology at the Pasteur Institute, and after a stay at the Salk Institute in the US he became a CNRS research director. In 2004 he published the genomic sequence of the mimivirus, the first of a series of giant viruses (giruses) that have since been discovered, and which have revolutionised microbiology.
What is a virus?
We used to think we knew. Before we discovered giant viruses, size was central to the definition of a virus: 0.3 micrometer filters were used to isolate microorganisms, and anything smaller than that which was infectious, was a virus.
So giant viruses were a bit of a surprise?
We discovered them by mistake. No biologist studying viruses could have discovered them, because the first thing they did was to discard anything that wasn’t filtered. We were working on intracellular parasitic bacteria when a 10-year old water sample arrived at our laboratory. It was thought to have been the cause of a pneumonia outbreak, but nobody had yet been able to isolate the microorganism responsible. Someone at our lab had the idea to use electron microscopy and there it was! It was infecting an amoeba but it didn’t look like a bacterium, although it was really big.
How big are giant viruses?
They can be 30 times bigger than the average virus, up to 750 nm. You can even see them with a light microscope! And their genome is larger than that of many bacteria. When we sequenced the mimivirus we were also surprised to see it was genetically very complex. It has 1018 genes, including many related to translation. These are not supposed to be present in viruses, since viruses use the host machinery to translate their genome into proteins.
That must have been a shock.
It was revolutionary, and it raised a lot of questions. With such complexity, could we still say that viruses are not alive? Recently researchers have found the first virus that can be infected by another virus – I say, if you can get sick, you are very definitely alive!
How do giant viruses change our view of evolution?
They are very old and the genomic analysis of marine viruses shows that they are very common and probably major players in the ecology. Although they are different from other viruses, if one analyses their evolutionary relationships, giant viruses fit perfectly with other viruses. However, they also have things in common with bacteria, such as the structure of the capsid, as well as with eukaryotes.
They are a real mix then?
My controversial theory is that DNA was invented by viruses to protect themselves from their host, an RNA cell. Slowly, the cell took that DNA machinery and incorporated it, and the nucleus was formed. At the same time, the viruses started to lose some of those genes that the cell had incorporated. After several cycles of infection, the cell gradually increased its complexity and the viruses reduced their genome.
Have we seen it all?
I think we will find bigger viruses, with more translation genes. One day we will have a real problem defining a virus!
El·lipse: Spanish science suffers a 25% cut in the budget
The May 2012 edition of the PRBB newspaper, El.lipse, a monthly bilingual newspaper, is now available: http://bit.ly/KprWYh
Is working at night harmful? This is one of the issues that the group of Manolis Kogevines (CREAL) is addressing in its research as explained in the new issue of El·lipse. You could also learn about the cutting-edge work with cord blood stem cells for transplants by Nadim Mahumd from the University of Illinois. The genetic origin of Afghanistan’s ethnic groups, the results of the most ambitious genetic study so far about osteoporosis and a European map of mental disorders are among the news that can be discovered in this month’s newspaper. But you could also learn about the book exchange initiative at the PRBB and also how to make a delicious aubergines “a la parmigiana” meal. Don’t miss it!
Studying Drosophila sensory behaviour – Matthieu Louis (CRG) explains
Studying Drosophila sensory behaviour – Matthieu Louis (CRG) explains
This is the first of a series of short (1-2 minute) videos explaining the research taking place at the different laboratories located at the PRBB. The group leaders themselves explain in a simple way what they are studying in their group.
In this video you can hear Matthieu Louis from the CRG (Centre for Genomic Regulation) talking about his research on Drosophila neuroscience and sensory behaviour. Check it out!
The New Cajal Era
The New Cajal Era
More than 100 years have passed after the first contributions made by Santiago Ramón y Cajal to the neural network theory. Nowadays neuroscientists take advantage of innovative tools to study neural circuits in order to understand complex behaviours.
This image by David D’Amico, from the group on neurobehavioral phenotyping of mouse models of disease at the CRG, shows the hippocampus of a transgenic mouse expressing yellow fluorescent protein (YFP) in specific subsets of central neurons. This type of tansgenic mice help scientists to understand neural networks in both physiological and pathological conditions.
“We have only one chance to develop a brain”
An interview published in Ellipse, the monthly magazine of the PRBB.
Philippe Grandjean, Adjunct Professor of Environmental Health at Harvard University, delivered a lecture in Barcelona invited by Jordi Sunyer, from the CREAL, a ‘model institution’ according to Grandjean. Sunyer introduced the talk about what the Danish-born scientist calls a ‘silent pandemic’: the effect of chemical pollutants on neurodevelopment.
To what extent do in utero conditions affect adult health?
There are several studies that show that exposing pregnant women to mercury can affect the development of their children, even if they are not affected themselves. Minamata disease, a neurological syndrome caused in children whose mothers suffer severe mercury exposure, was discovered in Japan in the 1950s, and was a shock to the world. Since then many other studies have demonstrated the effect of mercury exposure on foetal development. However, it wasn’t until 2009 that an international agreement was reached to control mercury emissions into the environment!
How many pollutants can be neurotoxic during early development?
There are about 100,000 chemicals in the world. About 200 have been documented as being neurotoxic to adult humans, and only five to foetuses: lead, mercury, PCBs (polychlorinated biphenyls), arsenic and toluene. However, the foetal brain is much more sensitive than the adult one! So I think we are only seeing the tip of the iceberg. For example, many pesticides can be neurotoxic to humans, as the nervous system of the insects that the pesticides attack is very similar to ours. For example, we did a study in Ecuador on pregnant women working in flower plantations, who were exposed to pesticides. Their children at school age presented a delay of up to two years in their brain development.
Are these effects irreversible?
The brain has great plasticity, so one might think that with enough effort we could get kids with lower cognitive abilities to catch up with the rest. But the problem is for this plasticity to occur your neurones must be in the right place. You cannot develop your full potential if you don’t have the correct anatomical foundation and if your nerve cells and connections are abnormal.
And does mercury exposure cause anatomical problems in the brain?
Normally we have no way of checking, but with Minamata disease, quite a few of the children died, and when they were examined at autopsy it was seen that their brain cells appeared in a disrupted pattern, as if their migration during brain development had been affected. So yes, we think so.
If they are so dangerous, why are these pollutants not banned?
The problem is that chemicals are not banned unless it’s proven that they are dangerous. But then it’s too late! I think we need to move towards the opposite strategy: a chemical should be banned unless it is proven not to be dangerous to brain development. Prevention should come before science. After all, we have only once chance to develop a brain.
Little big fly
Little big fly
In this photo taken by Cristina Morera Albert, of the CMRB, a house fly is observed with a scanning electron microscope (SEM). This type of microscope uses electrons and electromagnetic lenses to “illuminate” a sample allowing visualising the sample in 3D at high magnification.
In this case, we observe the compound eyes of the fly and its thorax, which is divided into three segments: prothorax, mesothorax and metathorax. The thorax is covered by hairs called bristles, which are always arranged in the same place and have a sensory function. One can also see the wings, which protrude from the second segment, with their nerves.
Converting stem cells into gametes is the most difficult transformation
Cristina Eguizabal came from Cambridge, UK, to the CMRB two and a half years ago to try to get male haploid cells (spermatozoids) from human pluripotent stem cells. She uses both human embryonic cells (hES) and induced pluripotent stem cells (iPS). The first are obtained through fertility clinics from unused fertilised embryos. The hES are isolated from the embryos and derived into cell lines at the Stem Cell Bank of the CMRB, on the 4th floor of the PRBB, where Eguizabal is working under the coordination of Anna Veiga. iPS cells, on the other hand, can be derived in vitro from skin cells or cord blood, as was shown recently, although the protocol is not optimal and these cells are not yet safe for clinical use.
Once she has the pluripotent stem cells in culture, Eguizabal tries to find the best conditions to differentiate them into primordial germ cells (PGC), which can then give rise to the spermatozoids or oocytes. What would be the practical applications of this, if it works?
Giving hope to parents
The simplest would be to allow people who are sterile to have children with their genetic characteristics. Currently, a sterile man depends upon anonymous semen donations to have a child. With this technique, a simple skin biopsy could lead to the creation of his own iPS cells, which would be differentiated in vitro into PGCs and which would give rise to sperm with his DNA which could be used in “in vitro fertilisation” (IVF) to have his child.
Another related application would be to allow people to have children free of a genetic disease which they themselves suffer. In this case, the procedure would be the same, but once the iPS cells were obtained, their genetic error would be corrected. This would be possible for well-studied monogenic diseases, caused by a single gene, such as cystic fibrosis or Duchene muscular dystrophy.
Many steps to go
“This won’t be happening for 10 or 15 years”, predicts Eguizabal. “Apart from the step I am working on, the differentiation of the iPS cells into PGCs, of which very little is known, all the other steps in the process need more research. For example, deriving the iPS cells from skin cells needs to become safer, as at the moment one of the genes included in this transformation is an oncogene, which could lead to cancer. The genetic correction of the iPS cells is also something people are working hard on”, continues the researcher. Both of these issues are also studied at the CMRB.
The differentiation of stem cells into sexual gametes, spermatozoids and oocytes, is the most difficult, much more so than getting stem cells to become neurones or cardiovascular cells, according to the Basque biologist. “First of all, the sexual gametes are the only cells that go through meiosis, a type of cell division that implies losing half of your genome. And secondly, their aim is to give rise to a living being, so their genetic and epigenetic information must be 100% correct”, she says. During normal physiology, germ cells suffer a huge epigenetic re-programming: their whole genome is methylated and de-methylated again. Methylation is a reversible modification of the DNA which affects gene expression. And in order to get functional gametes, it is important to reproduce this methylation in vitro. But it is not easy. Eguizabal plans to use molecular techniques such as bisulphite sequencing to check the methylation status of the DNA once she gets the cells she is interested in.
This article was published in the El·lipse publication of the PRBB.
“At the PRBB you have created the right atmosphere and spirit”
An interview recently published in Ellipse, the monthly magazine of the PRBB.
Hermann Bujard was from 2007 until 2009 the director of the European Molecular Biology Organisation (EMBO), which started 45 years ago with 13 member states and now has now up to 27. Bujard has worked both in academia and in industry, having also been scientific director at Hoffmann La Roche. Now currently working on malaria, he visited the PRBB and told us about his vision of science.
EMBO has played an important role in the development of modern life sciences in Europe. We identify and support postdoctoral fellows and young group leaders around the world, and we organise meetings and publish some journals. We only have an annual budget of only 16 million €, but we offer quality and support to individuals. We have created a network of excellence throughout Europe: if you look at the CV of any high quality life scientist in Europe, at some period in their career they will have been involved with EMBO. And this network leads to many cross-border collaborations.
What is the situation regarding female researchers?
This is a long-standing issue at EMBO, and a difficult one. More than 50% of students are female, while at the senior level women occupy only 15% of the positions. I think the research careers are such that we select against very precious good and original people, not only women but also men. It’s a very tough The competition is very tough, and by the time you get a 5-year position you are 37 and you might want to have a family, but you still have a lot of insecurity and a low salary. In addition you have the publishing pressure. Many women who would be very capable scientists just don’t want to go down this road. And we have to think whether we can afford to lose 50% of our creative brains.
What is the solution?
I think that we should look at the whole career of the person and not only their publications. At the moment, we select people who publish a lot, but they normally do mainstream research. and these usually do research on the main stream. There are researchers that are good and original thinkers and may publish only one paper every two years, but each of them is a seminal piece of work. And yet, we select against them. We are too much success-oriented in the short-term. Instead, we should ask the applicants for their four best papers, read them and decide if the person has good ideas.
What has changed in European science in the last 15 years?
Spain is my favourite country to exemplify that change. 15 years ago people from Spain only applied for fellowships to leave, while today many people apply to come to the new centres of excellence in Madrid or Barcelona, and not only Spaniards, but people from the UK or America. And this is a success of structure: highly valued scientists have introduced a critical mass of people working together in a departmental structure which is very good for small and young independent groups.
For example, what you have established here at the PRBB is very close to how things should work. The founders of the park created a spirit that can be seen in the way people behave. When you select very good group leaders, you get good postdocs, good students. And good people are not shy, they communicate, are open to discussion. I think this atmosphere exists here.
