The major scientific discovery of the year according to PRBB researchers

Every year there are hundreds of new scientific discoveries made in the world, many of them small steps, others bigger. Now that we reach the end of 2009, I have asked researchers of the different centres at the PRBB what has been, in their view, the most exciting scientific advance in their field. Their replies (below) were published in the 29th issue of El·lipse.

 PROTEOMICS
Toni Pascual (IMIM-Hospital del Mar)
“Christian Reichel from the Austrian Research Centre and a proteomics and doping researcher, has discovered that the SDS universally used in SDS-PAGE to separate proteins by their molecular weight, also binds to polymers such as polyethylene glycols, modifying their migration and making their recognition by antibodies more difficult. The use of sarcosyl instead of SDS avoids this problem. This finding is very relevant given the very frequent presence of these polymers in recombinant drugs”




HUMAN GENETICS
Ben Lehner (CRG)
“Over the past year there has been a bit of a revolution in human genetics, and many variants have been discovered in the genome that influence the risk of common diseases such as cancer. The identity of these variants has the potential to tell us about the biology of such diseases, but in nearly all cases they only have a tiny overall effect on disease. This tells us that we still do not understand the genetics of complex diseases and traits - for example why tall parents have tall children. It's rather humbling considering the amount of money that has been spent.”



EVOLUTION
Arcadi Navarro (CEXS-UPF)
“One of the most remarkable discoveries of the year has been the description of a new hominid species, Ardipithecus ramidus. The discovery has everything: it gives us information about a part of our phylogeny that is very close to our common ancestor with chimpanzees and of which we had few fossils so far; confirms once more that Darwin was right; and it has been the subject of the usual media manipulation by the creationists. In Al-Jazeera they have showed a documentary in which they explain that “Ardi” “demonstrates” that the man does not come from the monkey. Spectacular!”


STEM CELLS
Núria Montserrat (CMRB)
"The reprogramming of umbilical cord cells has been one of the major advances this year, since it opens the door to the future cell therapy. These cells, because they are so young, have not had time to accumulate possible mutations and they are immunologically immature, which minimises the risk of rejection. Also, they can be reprogrammed in a short period of time and without the need to overexpress the oncogenes that so far have been used. All this makes me think they might be an optimal source for future studies in cell therapy and regenerative medicine”.


EPIDEMIOLOGY
Jordi Sunyer (CREAL)
“Peter Gluckman, from the University of Auckland, has demonstrated how environmental influences during mammalian development lead to stable changes in the epigenome that alter the individual's susceptibility to chronic metabolic and cardiovascular disease, acceleration of pubertal timing or impaired cognitive development. Overall, it provides a model for how early life offers a potential point for preventative intervention.”

Superquick update

Wow, it's been a while! sorry for the delay. Not that nothing exciting has happened here at the PRBB.... since June: quite on the contrary! Here's a brief summary of some of the highlights, with links elsewhere for lack of time to write about them all now...

OPEN DAY: It took place on Oct 4, there were thousands of people visiting and they all enjoyed it very much! You can read some stories about it here or in the Science meets society blog.

ELLIPSE AWARD FOR SCIENCE POPULARIZATION: This was the first year we organised this prize. It wasn't supersuccessful (how difficult things tend to be to start with...!!), but I am quite pleased with the turnout, there were pieces in Engilsh, Catalan and Spanish, and such varied formats as poetry, theather scripts, comics, or narrative. If you don't know what I'm talking about you can refresh your neurons reading this earlier post. And to have a look at the winners you can check the award's website award's website.

OK, there's plenty more things, specially more science related, but I'll leave it here for now.

Take care!

More Intervals videos

Remember a previos blog entry where I told you about some videos thatpeople at the PRBB had done in the Intervals course "Visual story telling – an introduction to film-making"? Well Eric May gave another edition of this course on 25 March & 27 May and there's some new videos.

Check them out, some of the are really good!!!!!

Click here to see the videos!!!

"Parallel realities": giving voice to people with Down Syndrome

Hi there,

This is a message from Mara Dierssen, a group leader at the
CRG (you can find more about her research on her website or read an interview I did to her for El·lipse, the PRBB monthly journal).


Anyway, I believe I have already mentioned previously she is my hero (look here and here for previous posts on other things she has organised). This time it is about an initiative she has been involved in to give a voice to people with Down Syndrome. Please read below and support this initiative!!!

--------------


The Catalan Down syndrome Foundation in collaboration with the Institute of Culture of Barcelona and the General Society for Authors has published a Music CD in which 10 people with Down syndrome have written the letters and collaborated in composing the music of 10 songs and are as well the actors of a video clip.


Neglect and exclusion are still too common in our society. With this we hope to increase the visibility and public recognition of the capacities of the Down syndrome people in a context of normality.


However, we need your help.

Please click in this Youtube link since this will help a lot this project!!!! You can click once a day to sum!

http://www.youtube.com/watch?v=KO7O3GtiUUw.

Also, please help us to give visibility to this initiative by sending this link to all your friends!

And finally, you can buy the CD at FNAC or El Corte Inglés or by emailing: direccio@fcsd.org :)
All the money obtained by the sales of the CD will go to the Catalan Down syndrome Foundation.

Thanks very much in advance!

Fundraising for the Abruzzo earthquake

During this week of May 4-8, a group of Italians from the PRBB have organised a series of activities in order to raise funds for those affected by the Abruzzo earthquake.

1) Italian dishes: in cooperation with the PRBB restaurant, for a week PRBB residents will be able to taste genuine Italian recipes at lunchtime. They will have to pay a little more for it, but all the money will go for the fundraising.

2) Raffle: Residents can buy the raffle tickets for 3€ at the reception of the 4th floor. The first prize will be an Italian cook coming to the winner's flat one night to prepare a delicious dinner!

3) Breakfast: on Monday 4 from 9am to 11am, on the 5th floor terrace, our Italians offered a fantastic Italian style breakfast for a good prize. It was so successful they are doing it again tomorrow, Friday 8.

3) Final party: on Friday May 8, and in order to finish the solidarity week, we will have a party at the inner square of the PRBB, with live music, batucada and the draw for the raffle.

Well done the Italian community for this good initiative! Will post some pics of the events later on and will let you know how much we raised!

"The illusions of the brain" Fair in Barcelona

So many things happening this week! Write this one down in your agenda.

From 10am to midnight on Friday May 8 you will be able to participate of talks, projections, experiments, concerts, a tennis table show and even a magic one... everything in the framework of a fascinating scientific trip.

This is the fair “Illusions of the Brain” (davinci.crg.es/ilusiones), which is organised by the CRG (one of the centres at the PRBB), open to the public and free.

Some of the highlithgs will be:

- the presentation of the CD “Realidades paralelas” (Parallel realities), a CD with songs whose lyrics have been written by teenagers with Down Syndrome.
- a scientist will explain to us why we were not able to detect the magic tricks a magician just did.
- the European table tennis champions will play an acrobatic game and a scientist will explain to us how their brain has spetial spatial capabilities
- several experiments in which we will be able to hear people coming who don't exist, to do a virtual race only with our mind, etc.
- a talk about the biological bases of beauty
- and much more!


It will take place at the Nau Central de Fabra i Coats. Schools do need to reserve in advance calling 93 316 01 00 or emailing comunicacio@crg.es.

Presentation of the Health Impact Fund

Thomas Pogge, from Yale University, came today to the PRBB to present, for the first time in Spain, the Health Impact Fund (HIF). This is an interesting initiative of the Incentives for Global Health (IGH)
Incentives for Global Health (IGH), a non-profit organization, and its aim is to stimulate research and development of life-saving pharmaceuticals accessible to the world's poor.

I believe that this is an issue of global importance, and so I was a bit disappointed to see the PRBB conference hall was not very full at all. But then I am often disappointed by this fact…

Access to medication in poor countries is a big problem. Not the only one leading to poverty and disease in these countries (there’s the lack of drinking water, corruption, etc.), but one that should be preventable.

There are two main related issues that affect accessibility to drugs nowadays:
- the innovation problem: that is, the fact that there is little R+D+I investment in diseases that affect mainly the developing countries. In fact, out of the 1558 new drugs developed between 1997 and 2004, only 21 were for tropical diseases and tuberculosis.
- the access problem: that is, that the price of patented drugs is too high for many people (specially in the developing world) to pay

Both problems are related since, if prices of drugs go down so that everyone has access to them, the return for the pharma companies is lower and they are therefore less interested in spending money in innovation.

The Health Impact Fund (HIF) presents itself as a long-term sustainable solution to continue innovation in the drug market without impending access to the medicaments. The idea, as I understand it, is the following.

- When a new drug is developed, the company can choose to register it with the HIF, rather than applying for a patent, as they currently all do.
- By doing so, they compromise themselves to sell the drug at cost-price (that is, to not make any money from the selling of the drug to the patients).
- In exchange, they will receive money from the HIF during the next 10 years. That money will be a share of the total HIF fund, which is expected to be about 5 bilion €.
- The amount of that share will be calculated annually, and will be proportional to the drug’s global health impact (understood as how much is that drug improving people’s lives).
- The total amount of the fund will be financed by governments. Other agencies, funds, etc. could also participate (e.g. Gates Foundation), but governments are the only ones that can commit for a long-term funding, which is needed to give the industry
- After the initial 10 years, the company must offer, at zero cost, global licenses on all the intellectual property required for the manufacture and sale of the drug, so that from then on anyone can manufacture the drug.

After Dr Pogges’ talk there was a round table that included members from pharma companies, NGOs, the Catalan government, researchers, and patent experts. Some of the questions and concerns raised there were:

- How would the price of the drugs be decided? Who should participate in this decision? Should the pharma companies be involved, or should it be independent assessors?

- How would it be decided what health impact each drug has and what percentage of the fund they are therefore entitled to?
o an important role of the HIF will be actually to collect lots of data regarding this – actually 10% of the fund would be used for following specific drugs, see who takes it and what are the consequences, etc. These data would be useful not only for the HIF but for lots of NOGs, international agencies, etc. interested in the health situation in poor countries.
o The idea is to check the real impact of the drug, and to give money back to the industries based not on ‘how many drugs they sold’ but on how much those drugs improved the condition of patients. This means (and this is an interesting point) that it would be in the interest of the pharma industries not only selling the drug, but also making sure that they are well prescribed, taken properly (a big problem in these countries is that people don’t take the drugs for the amount of time necessary, etc.), etc. Some ways in which the industry could help with this is writing instructions in the local languages, offering courses to local doctors and nurses, collaborating with NGOs and international agencies who work locally, etc.

One question I have is: would the pharma companies be really interested in this? I don’t see them making more money with this initiative than they currently make, so why would they decide to go for HIF? One suggestion that came from someone at the audience was to create a ‘HIF’ stamp that would give companies quality/moral value that would make them more attractive to costumers (similar to having a ‘fair trade’ stamp, or ‘organic’, etc.). I am not sure that would work for medicines, but it’s a good idea…

There were many other things discussed, and many more that were remained unspoken, but if you are interested you can check more about this initiative in the Health Impact Fund (HIF) website. At the moment Thomas Pogge is travelling the world talking to all the potential stake holders (governments, scientists, pharma companies, NGOs, lawyers, economists, philosophers, everyone!), presenting the initiative and collecting all the possible feedback to improve the proposal.
I hope that soon we will see a final HIF proposition that responds to everyone’s concerns and that can help, finally, making good drugs accessible to those who need them.

What's behind our genes? Come to La Pedrera to know!

AND... before I forget, there is something else happening next week. The next cafè científic organised by the Science meets Society (SmS) group at the PRBB will take place next Wednesday May 6 at 7’30pm at La Pedrera (a beautiful Gaudi building).

The subject discussed will be how can organisms as different as a fly and a human come from very similar genome? The experts who will help discussing this will be Juan Valcarcel, from the CRG and Jaume Bertranpetit from the CEXS-UPF.

There will be some snacks and drinks. Do not miss it!!


Title:     What's behind our genome?
Speakers:  Juan Valcarcel & Jaume Bertranpetit
Where:     La Pedrera
When:      Wednesday 06 of May at 19:30
 

Making medicines accessible to the world's poor

Hi there,

for once, I am announcing something BEFORE it happens...! I really am going to get better with this blog, I promise!

Anyway, this is interesting and important.

Next Monday May 4 at 12 o’clock at the conference hall of the PRBB, there will be the presentation of the Health Impact Fund for the first time in Spain.

The presentation will start with a talk by Thomas Pogge, from Yale University, entitled: “How to make pharmaceuticals that are accessible for the whole world?”. The talk will be followed by a round table chaired by Joan Josep Moreso, vice-chancellor of the UPF. Other participants at the round table will be members of NGOs, etc.

The Health Impact Fund is an initiative of the Incentives for Global Health (IGH), a non-profit organization, and its aim is to stimulate research and development of life-saving pharmaceuticals accessible to the world's poor.

I will certainly go to the talk and will try my best to give you a good summary afterwards.

A VERY special Sant Jordi: love is in the air!

Every year, the PRBB residents surprise us with something new during the celebrations that are organised at the park for the whole community, such as the Christmas party, the Beach volleyball championship or the Sant Jordi celebration. We have been able to shout in rock concerts, to see a ‘capoeira roda’, to dance ‘sardanes’, to hear the angelical voices of the PRBB choir and even to enjoy a trapeze show, everything done by the residents themselves.

But when we thought we had seen it all... on April 22, 2009, we laughed and cried again. Apart from the traditional book exchange of the Sant Jordi celebration – this year more than 500! – and of the roses that filled the square, the PRBB theatre group, which exists since only four months, offered us the best that can be offered: a smile and a good time amongst friends.

More smiles, and even one or two emotional tears, accompanied the first public declaration of love – and what better day to do it? – to take place at the PRBB. The lucky girl (me!) was very surprised and emotional, altough she nearly killed the boy because of the embarrassment he made her go through. The about 200 residents that were witnesses of it had just finished enjoying the demonstration of the PRBB capoeira group, whose members (including the boy and the girl) showed the ability and agility they are acquiring week after week. Furthermore, continuing with the sports, the day finished with a raffle to choose which beach volley teams will have to confront each other in the next months.

Difficult to beat? Wait until the next party! (although I can't imagine what can come after this!!!!)

The PRBB organizes two 'science popularization' awards

For the fourth consecutive year the PRBB and the CEXS-UPF organize the “Premi PRBB de recerca en ciències de la salut i de la vida”, an award for the best research works by high school students in life sciences. This year the award is also open to the participation of VET (Vocational Education and Training) students in health and chemistry.

But this is not the only novelty of 2009. The PRBB wants to work not only with students, but also with scientists, housewives, lawyers, painters: with any person who is interested in science and wants to help in its communication. Thanks to the award “Premi El·lipse” they will be able to communicate science to the general public, be it by words or graphically. This year, the theme of this new award will be stem cells. So if you have ever wanted to write a theatre script about a cancer patient that receives stem cell therapy, or to create a comic about the life of a researcher working on this field, this is your opportunity! The written material can be in Catalan, Spanish or English.

For more information on both awards please see www.prbb.org/premi and www.prbb.org/premiellipse. The deadlines to send your work are April 14 for the “Premi PRBB” and September 1 for the “Premi El·lipse”. Amongst other prizes, you could win a laptop for the best research project or €1000 for the best science communication work about stem cells. Good luck!

Theatre and science!!

Building up on the previous social activities at the park, a theatre group has just been created at the PRBB. For now we are getting started, doing exercises to let go our bodies, to increase trust in our colleagues, etc. Soon we will do some lessons of interpretation and finally we will prepare a theatre play to present during this year’s PRBB Open Day (which will be on the 6th of June – note it down!).

The piece we will interpret that has already been represented, driven by the Museum of Natural Sciences. It is about Darwin and the Oxford evolution debate. We have the same director who has directed the play previously and she is the one teaching us. Her name is Verónica, she is from Chile and she’s good!

We are rehearsing every Tuesday from 6 to 8pm at the inner square offices (the same offices, incidentally, in which PRBB residents can also enjoy choir rehearsal on Mondays and capoeira lessons on Thursdays!).

“The world is ours””

This is an interview with Dr. Paco Real, who used to be at the IMIM-Hospital del Mar. This interview appeared in the second issue of El·lipse, which by now you must already know is the PRBB's monthly newspaper.

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Dr. Real was born in Barcelona, he studied medicine at the UAB in Bellaterra and worked at the Memorial Sloan-Kettering Cancer Centre in New York for 7 years. From there he moved back to Barcelona, nearly 20 years ago, to coordinate what today is the Research Unit in Cell and Molecular Biology at IMIM. He studies the molecular mechanisms of pancreatic and bladder cancer, he is a professor at UPF and the father of an 8-year old girl, and he loves music and reading.


How did you end up doing research?
When I was 12 I had a neighbour on the third floor who was an immunologist. He used to talk about “-bulines” and I always wondered what the first nine letters, “immunoglo“, which I could never hear properly, meant… When I discovered it, I studied medicine at the UAB in order to do research in immunology. Later, while receiving lessons at the Hospital de Sant Pau, I met two excellent doctors who made me become also interested in clinical medicine. Actually, I was very fortunate in having two real mentors, one in the hospital (César Díaz) and one in the lab (José Luis Rodríguez); most people have none. They both offered me their time and knowledge, and I will never forget that…

Then you left to New York...
Here it was very difficult to do research and practise medicine at the same time, so I rejected my resident medical post and I left to the US. There I was doing my PhD in cancer immunology at the Memorial Sloan-Kettering hospital, and at the same time I could undertake clinical activity.

You came back to Barcelona to join the IMIM in 1988 – why?
Because I did not want to spend all my life thinking that perhaps one day I should come back home. I was still young, and I decided to give myself 4 years to see if I could make things work out for me here. On January 6, 1992, exactly four years later, I started adding and substracting, and the final result was positive; and so here I am.

How was coming back?
They were very interesting years. IMIM had existed for years, but it had stopped working for years, too! We had to do several reorganizations and we got great help from both the people who were already at IMIM and the new arrivals. The situation has now changed a lot; the PRBB was something completely unimaginable back then. On the ‘Three Kings’s day’ in which I arrived back to Barcelona I could have never thought of asking for such a present!

But you stopped practising medicine?
At the beginning I did some work at the Hospital del Mar, but I don’t anymore. But every time I see a doctor talking to a patient I am very jealous. And my research is completely conditioned by my medical education. When I do research, I think of diseases, not molecules.

And you have also stopped doing bench work…
When I am here that’s the case, yes, the group has grown a lot and it requires lots of time. To do some experiments, I have left on a sabbatical a couple of times, to France and to the US. It’s a humility lesson that every scientist should do; you see how experiments don’t work out and then you understand your poor PhD students.

What is the best and the worst of being a scientist?
The best, that you are free and have no limits. The worst… that you are the limit! But then you can always collaborate.


What would you be if you were not a scientist?
I can see myself doing many different things, but I think I would like to be a bookseller of the type that don’t exist anymore, those that read a lot of books and discuss them with their customers…

Which has been the best moment of your scientific life?
It hasn’t arrived yet (I hope!); it’s always tomorrow.

Studying the effect of drugs in humans

The clinical research group in human pharmacology and neurosciences of the pharmacology unit at IMIM-Hospital del Mar, directed by Magí Farré, has been studying both the physiologic and mental effects of drugs of abuse, such as ecstasy (MDMA) or cannabis, for more than 20 years.

They do cardiovascular and motor activity performance studies, as well as arterial pressure measurements and blood analyses to learn about the pharmacokinetics of drugs; how they are metabolized and distributed, etc. The mental effects are studied through questionnaires and behaviour studies, as well as by PET (positron emission tomography) and FMR (functional magnetic resonance) of the brain. These are done at the IAT, located also at the PRBB. The unit, which has 12 beds on their premises, also does phase I and II clinical trials to check the efficiency and tolerance of new drugs.

All the studies must follow a clinical assay protocol, which can take between 5 and 12 months to be accepted by the local Ethics Committee for Clinical Research and by the Spanish Drug Agency. The studies must also be double-blind: neither the patient nor the scientist knows whether the patient is taking a drug or a placebo. According to Farré, there are often surprises that exemplify the important role played by the mind. For example, in a study done years ago by Jordi Camí, founder of this laboratory and currently the director of the PRBB, it was demonstrated that the manipulation of the expectations – to think you are taking a drug when you are not, or the other way around – was as important than the real effect of the drug.

Some of the current studies of the laboratory, which can last from one single day to a whole year, are about the effects of recreational drugs in the inhibition of the metabolism of medications. Other studies are about how some genetic mutations can make the drugs affect us in different ways, or about the different effects of ecstasy in men and women. According to Farré, the most important contribution of the group has been in the ecstasy field, in which they have done things that had never been done before. Another characteristic of the group, nearly unique in the world, is that pretty much all the research process is done in humans; the substances are administered in humans and their effects, the drugs concentration and their metabolites in different biological fluids are measured.

The clinical assays laboratory, apart from their own studies, also offers services to third parties, including pharmaceutical companies such as GSK (GlaxoSmithKline). They also collaborate with the psychiatry and drug addiction service of the Hospital del Mar, and with Jaume Marrugat, director of the research program on inflammatory and cardiovascular processes. With him they do studies about nutrition, such as the effects of the antioxidants in olive oil or wine.

Neurons derived from mouse embryonic stem cells

This picture appeared in the 14th edition of El·lipse, the PRBB monthly newspaper.

This picture, taken by my good friend Sabrina Desbordes, of the hematopoietic stem cell biology and differentiation group at the CRG, shows colonies of neurons derived from mouse embryonic stem cells (mESCs) using specific common protocols. Neurons (seen in green) are obtained after two weeks of differentiation on stromal cells, which confer a neural fate to mESCs. Using adequate cytokine cocktails, different neuronal cell types can be differentiated. The nuclei of the cells are stained in blue.

“Being a scientit is a way of life”

This is an interview that appeared in the 18th edition of El·lipse, the PRBB monthly newspaper.



The daughter of a painter and a neurosurgeon, Mara Dierssen has always known what she wanted to be. This 46-year old researcher is the head of a leading research group in neurobiology at the CRG, teaches at three universities, organises many outreach activities, sings in a rock and roll band and has four sons.


When did you become interested in science?
You can tell a scientist from early on, we are the ones who always want to know everything... I was always fascinated by the nervous system, specially the big questions such as how do we keep memories, or why we feel emotions. After studying Medicine I did my PhD at the University of Cantàbria in neuroscience.

After a postdoc at the UAB I went back to Cantàbria to start my own lab. I started from scratch, but soon people arrived to work with me in mental retardation. It was a very productive period.

And then you came back to Catalonia...
Yes, to the Institut de Recerca Oncológica with Xavier Estivill, who had a very potent group in the genetics of Down syndrome (DS). These years were very good and I learned a lot.

From there you came to the CRG. What are your main research lines?
We basically study mental retardation, specially DS, and also neuropsychiatric diseases.

You are very much in contact with the people who have the disabilities you study – how do you value this?
We scientists cannot be detached form the reality we are studying. For me it is important to know that there are real people behind my research. And getting to know them helps one to understand better the disease. Also, I think we have a lot to learn from people with disabilities, from their attitude and willpower.

It seems impossible that you have time to do everything – how is your typical day?
Tiring! I wake up at 4’45 am and I come to work: articles, meetings, experiments, classes, paperwork. I eat something quick in front of my computer and I try to leave at about 17’30 or 18h. When I get home I help my sons with their homework, we have dinner, chat a bit and I go bed at about 11’30 pm.

Do you think that research is an egalitarian world?
I think we are getting there, but it isn’t yet. The big decisions are still in hands of men, who occupy the majority of top positions. When I started it was even worse: before getting a contract they asked you whether you were thinking of having children, and that was a decisive factor!

What do you think about science communication to the public?
If we want science to be valued and to receive funding from public sources, we cannot ignore the public. And, if it is properly explained, people love science! It also favours scientific vocations. A few people have come to do some experiments in my lab after having attended a science outreach event.

The problem is that this is not valued in Spain, it is rather considered a waste of time. Also, it requires a lot of time and effort and, in an environment with so much pressure, this is difficult. And there is zero economic support. It is a real misery compared with what is dedicated to other social or cultural events.

What is the best about science?
The intellectual challenge! The satisfaction of understanding a process, having to revise my own thinking every five minutes because there is something that doesn’t fit.

And the worst?
The job insecurity, which doesn’t allow us to start ambitious projects. I had to start my lab five times, and I didn’t actually have a contract until I was 40: I had only fellowships. Of course mobility is a positive thing, but a balance is necessary.

What would you be if you were not a scientist?
I would just not be! Being a scientist is not a profession, it is a way of life.

DNA uncovers your geographic origen

An European woman, a Yoruba man, a Japanese child. Which historical and demographic events explain the genetic differences between human populations? Two of the genetic markers that are most used to study human migrations are the Y chromosome and mitochondrial DNA (mtDNA), a type of DNA found within the cellular organelles called mitochondria. These are the only two types of DNA that do not undergo genetic recombination, a phenomenon in which the DNA sequences coming from the mother and the father mix up. The Y chromosome is transmitted intact from the father, and the mtDNA comes always from the mother. The fact that they come always from one parent only makes it much easier to follow their lineage.

Thanks to these markers we know about the large human migrations, such as the colonisation of America and the islands of the Pacific, or the migration out of Africa that took place about 60,000 years ago, first to Asia and Australia and then to Europe and the American continent. We also know that the mtDNA is globally more homogeneous than the Y chromosome. This implies that, contrary to what is usually assumed, women have migrated more than men. This global migration pattern can probably be explained by many small migrations due to the fact that women used to go to live to the regions where their husbands were from.

But there are still many local migrations to understand. For example, the research group on evolutionary biology at the CEXS-UPF has recently done a study on the Cuban population in order to see if there was an Amerindian genetic footprint left. They were the original population of the island, who were exterminated during the European colonisation. The results show that, even though there are no Amerindian markers in the Y chromosome, up to a third of the genetic background of the mtDNA is Amerindian. This implies that the colonisers had sexual relations with the Amerindian women before their total extermination.

And why is it interesting to study migrations? Apart from the purely historical interest, it is important for genetic epidemiology studies to know the structure of the current populations. For example, to determine if a common genetic variant in a population is associated to a disease it is necessary to first know whether this population is homogeneous.

Molecular language: how cells communicate

This is an article that appeared in the 5th edition of El·lipse, the PRBB monthly newspaper.

Communicate or die, that’s the law for cells. Cells need to be aware of what’s happening in their environment and react accordingly. For that, they have very complex signalling mechanisms, which, unless the signal is diffusible, tend to start with a receptor protein located at the membrane of the cell (what separates the cell from its surroundings). This receptor senses a signal from the environment and then triggers a cascade of proteins that will activate other proteins, and so on; this is called a signalling cascade. In eukaryotic cells such as the human ones kinases and phosphatases - a type of proteins that add or remove a chemical group to other proteins and modify their activity - are frequent components of these signalling pathways, The signalling cascade will finish in the nucleus, the part of the cell where the DNA is stored, and will either activate or repress certain genes. The action of these genes will dictate the response to the initial signal.

The signals that trigger a reaction in a cell can be external, such as several types of stress, including starvation, heat shock or osmotic stress. However, the stress signal can be endogenous, as observed for oxidative stress: the use of oxygen during respiration can generate reactive species as a side-product, and these species can damage all types of biomolecules, including DNA.

Furthermore, cells also need to talk to each other in order to behave as a whole within the organism. These cell-to-cell signals can be through physical contact or through molecules that are released from one cell and captured by another.

The genome in a microchip

This is an article that appeared in the 4th edition of El·lipse, the PRBB monthly newspaper.

In the genomics world, the microarray is the king. Microarrays are 5 cm long and 2 cm wide slides in which up to one million microscopic drops can be placed next to each other. Each of these drops, which are chemically attached to the glass, forms a dot that contains a single probe – a piece of DNA that corresponds to a fragment of the genome. This way one can have a big collection of genes, even the whole genome, represented in a few slides. Microarrays allow scientists to do analyses in thousands of genes at once, analyses that would normally have to be done one gene at a time.

The most common of these analyses is the study of gene expression. Genes are “expressed” when they are activated in order to give rise to a protein, which will carry out the function specified by the gene. In this path from DNA to protein there are some intermediaries, the messenger RNAs (mRNAs). Each gene produces an mRNA, and the mRNAs are what scientists usually detect to know that a gene is being expressed. For this, mRNAs are isolated from cells, labelled with fluorescent molecules, and placed on the top of microarrays, where each mRNA will recognise its probe – the dot that contains its related DNA – and will bind it specifically. This way one can look at the microarray and see which dots are fluorescent; these will represent the genes that are being expressed.

With this system, scientists can find out which genes are expressed in a specific condition and at what level – according to the fluorescent intensity. They can also compare two conditions, by labelling the mRNAs from the different conditions with different colours. For instance, the gene expression of a healthy and a diseased person can be compared, or that of the same person before and after treatment with a drug. Knowing which genes are expressed in one condition or another gives hints as to which genes may be implied in the disease or what effect the drug has.

At the PRBB there is a core microarray service since 2001, directed by Dr. Lauro Sumoy (CRG). This service is used by several groups from the centres of the PRBB who work in very diverse fields, from molecular biology to evolution.

“Air pollution is a real health problem”

This is an article profiling Dr. Nino Kuenzli’s group at CREAL. It appeared in the 2nd edition of El·lipse, the PRBB monthly newspaper.

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The group directed by Nino Kuenzli is very “fuzzy”. As his research on health problems caused by air pollution is very interdisciplinary, he works with experts in epidemiology, statistics, genetics, molecular biology, exposure, aerosol and health sciences from all over the world.

Dr. Kuenzli’s current main project is testing the hypothesis that pollution causes atherosclerosis. He initiated a pilot study when he was in Los Angeles, in which he found a relationship between air pollution and the thickness of the arteries – a marker of atherosclerosis. He is now investigating this in adults in the Girona region. For this, he is collaborating with Jaume Marrugat’s group, from IMIM, and he’s using the 3,000 people cohort of their REGICOR cardiovascular study, which started in 2000.The images of the arteries are sent to Amsterdam where the thickness of the wall is derived. The air pollution measurements are done by Laura Bouso in Girona.

Dr. Kuenzli is also leading the air pollution group of the European Community Respiratory Health Survey (ECRHS), in which more than 20 centres around Europe collaborate; he and Raquel Garcia work in a Swiss study (SAPALDIA) to investigate the effect of air pollution on adult asthma; he is an advisor in EGEA, a French study on genetics and asthma; and he’s a collaborator of the most important air pollution study ever done in children, the Children’s Health Study of the University of Southern California (USC), in which thousands of children participate in lung function measurements every year since 1992. Maria Mirabelli, a collaborator of Dr. Kuenzli, is now investigating the impact of wild-fires on the health of these children. Moreover, Dr. Kuenzli and the USC team just started a further study on air pollution, atherosclerosis, and lung health with USC college students– the TROY study.

According to Dr. Kuenzli, Barcelona is too polluted even by the lax European standards, very car-oriented and with extremely dense traffic. “It has been shown that children who live within 100 m of dense traffic have more problems with lung development and asthma; this should be taken into account in urban planning and policy making”. Says Dr. Kuenzli: “It is estimated that if particles go up by 10g/m3, mortality increases by ~4%”. He and Laura Pérez, a risk assessor, are estimating the health benefits of the air quality management plan of the Generalitat. The target of the plan is to be in compliance with European air quality standards by 2010.

One of the most important developments in the field, explains Dr. Kuenzli, is the improvement in estimating people’s exposure to air pollution. There are now very powerful models available, in which measurements and geographic information are used to develop air quality maps. “In simple words: to know air quality at your home, we geocode your address and link your location to these maps”.

“Being a scientist is like playing football: when you work you play, and this keeps you motivated”

This is an interview to Jordi Mestres, a scientist working at the GRIB, a mixed unit of the IMIM and the UPF focused in bioinformatics and located at the PRBB. This interview appeared in the first edition of the El·lipse newspaper, which I am in charge of publishing every month.

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Dr. Jordi Mestres is from Girona, has lived in the United States, the Netherlands and Scotland, and three years ago he came to work at the PRBB as the head of the chemogenomics group at the GRIB. A year ago, he created the spin-off company Chemotargets, which develops new tools to identify active molecules for therapeutic targets. Jordi Mestres tells us how he arrived where he is.

When did you start being interested in science?
At high school. I also liked History, but I saw I could not change it…

You then decided to study Chemistry: why?
In chemistry not everything was established; and I could study it in my home town…

And you got in touch with the pharmaceutical industry….
During my PhD I did a 3-month stage at a company in Michigan. I thought it was interesting, because I had to develop new methodologies and what I was doing had practical applications.

You have worked in pharmaceutical companies for 7 years, then came back to academia. What are the main differences between both worlds?
In general, the best from the academic world is the environment that favours the generation of new ideas and the establishment of all type of collaborations. The best in industry is that projects are therapeutically very interesting and that you have access to great amounts of data and very generous budgets.

What made you come back and start a research group?
In Edinburgh we had our first daughter, Fiona, and soon pressure from the grandparents to have her close by was stronger than our desire to stay there…And work is not everything in life, neither is money! Here, despite a huge salary reduction, quality of life is very good: there’s sun everyday, the sea next by, and the grandparents who can take care of the children, and money cannot pay that! But we would consider leaving again, if circumstances changed.

What has been the most satisfactory moment of your career?
Perhaps the recognition, in 2000, of being the inventor of a series of molecules therapeutically useful, the first of the four patents I have. Lately, the concession of the Corwin Hansch Award in 2006 by the QSAR and Molecular Modelling international society.

Science: collaboration or competition?
Science in its pure state is honest collaboration, and this is when it is most enjoyable. But it is true that there is a lot of pressure to publish and to compete. In our case, however, it is very important to collaborate: what would we do with a perfect drug design without someone who can synthesize it and test it? Also, at the PRBB we have the luxury of being amongst 1000 people, many of them with a potential therapeutic target…

What is important to do research?
Curiosity, scepticism and good humour!

What would you be if you were not a scientist?
A musician, most likely. When I was a child I used to sing at the Escolania de Montserrat, where I studied piano and violin. But in harmony lessons at the Conservatory of Girona I used to do chemical reactions, and even though I have never left music, one day I had to choose. But I have never doubted my choice: I love my job.

Lost in translation?

(from an article in El·lipse, the PRBB monthy newspaper, published in January 2008)

The essential information for life is encoded in the DNA. However, it is mostly the proteins that make cells work. How do nucleotides, the basic units that form the DNA, transfer the information to the amino acids that form the proteins? This happens through two steps: transcription, the transfer of information from DNA to mRNA which occurs in the nucleus of the cell, and translation, the transfer of information from mRNA to protein which occurs in the cytoplasm. Transcription was thought for years to be the main mechanism to control gene expression, but translation has now been found to be more important than expected.

The genetic code specifies that each codon (formed by three nucleotides) in the mRNA corresponds to a specific amino acid. The transfer RNAs (tRNAs) are the molecules that execute this code by carrying an amino acid on one of their sides and binding to the corresponding codon on the other side. All this happens within molecular machines called ribosomes, which catalyse the reaction. Translation finishes when the ribosome faces one of three existing ‘stop codons’ on the mRNA. When this occurs, no tRNA can recognize it and the amino acid chain is released.

Most of the energy that a cell consumes is dedicated to the making of ribosomes and to translation, an essential process for life. Thus, it is not surprising that translation is highly regulated. For example, cell stress and physiology are controlled by the activity of the translation initiation factor eIF2alpha, which is modified under stress and ultimately leads to a response that changes the transcriptional profile of cells. This is one of the many examples in which transcription is under translational control. Failure of this control system contributes to diseases such as diabetes, metabolic sindrome, osteoporosis and neurodegeneration.

The life of a cell

All living organisms are formed from millions of micrometric units, the cells, which are constantly growing, reproducing and dying throughout the lifetime of an organism. The cell cycle is divided into the interphase – the time between divisions – and the mitotic phase, in which the cell divides physically. The interphase is formed by the growth stage (G1), the duplication stage (S), during which the cell duplicates its DNA, and the maturity stage (G2). After G2, the mitotic phase, which can be divided into 2 stages, begins. The first stage is mitosis, in which the chromosomes are shared between the two daughter cells. The second stage is cytokinesis, during which the mother cell divides physically. The cell cycle is ordered and strictly regulated. This regulation is essential, since the chaos of the cell cycle is the main cause of cancer: when there are errors in the cycle, the cells don’t stop dividing and the tumour grows.

At the PRBB centres there are many groups performing research into different aspects of the cell cycle. Among them are Dr. Gil’s group (IMIM), who focus on the biochemical connection between programmed cell death and the cell cycle regulation in mice, and the groups of Dr. Hidalgo’s and Dr. Ayté’s from the CEXS-UPF, who are trying to understand the control of the cell cycle in yeast, a model organism widely used in this field. Dr. Posas (CEXS-UPF) also uses yeast to study the control of cell progression by the protein Hog1 MAPK, whilst Dr. Muñoz (CRG) is interested in the role of MAPKs in the control of proliferation and differentiation of the muscle. Another group is Dr. Vernos’ (CRG), who study the chromosomes sharing during mitosis in frogs.