Interview with Xavier Salvatella – by Mark Peczuh

This is the first of several posts from Mark Peczuh that I am hosting. In this post, Mark interviews Xavier Salvatella on his research (protein-protein interactions and their implications for disease) and why he works/lives in Barcelona. Enjoy!

“It is a bit like Janelia Farm on the Diagonal”

We met, unexpectedly, at the entrance to his building in the Barcelona Science Park on the University of Barcelona campus. His building is literally in the shadow of Camp Nou, the home stadium of the famed Football Club of Barcelona better known simply as “Barça”. He was hurriedly arriving to make our appointment in the same way I was. Although it has been a few years, I instantly recognized Xavier Salvatella by his characteristic gait with the torso slightly askew and the welcoming smile. Xavier had reluctantly agreed to be the subject of my first interview – a guinea pig. I am currently in Barcelona on a Fulbright Fellowship. As part of this fellowship I will be interviewing interesting scientists here in order to understand the practice of science/research in the context of place.

Xavier Salvatella (Image Credit: Mark Peczuh)

MP: So tell me about your research.
We have two sides of the lab. One side has been focusing on methods development to characterize the flexibility of proteins. Everybody is aware of the importance of flexibility, but it’s very hard to characterize. Right now only simulations are undergoing a revolution. [This revolution] is based on a change of approach on how computers are built. Rather than building supercomputers that can do many different tasks, people have said, “Perhaps it’s better to build them for a specific task.” Computers have been optimized to do molecular dynamics on a much longer time scale, up to microseconds. The simulations still cannot be done with very large and complex flexible proteins and many things can not be studied with simulation.

MP: I’m expecting you to tell me something about how your group uses NMR as a tool for characterizing dynamics of proteins. How does the time scale of the experiment – either simulations or NMR – fit with the dynamics of the protein?
That’s a good question. By NMR you can look at dynamic processes at any time scale. Processes from nanoseconds, using relaxation times, to seconds or more, by doing experiments in real time, can be studied. Simulations can only look at the fastest time scales but there are many, interesting, dynamic processes that are so slow that they’re beyond the current reach of simulations. The encouraging thing is that on the fastest time scales, there is good agreement between the two. This has led to improvement of both of the methods (NMR and simulation).

MP: Where do protein dynamics come into play in biochemistry? Protein-protein interactions, catalysis, what?
Protein dynamics are definitely important to catalysis, but we’re focused on protein associations – either protein-protein interactions (PPIs) or protein oligomerization. Usually when PPIs are modeled via docking, they’re treated as two rigid bodies and the complementarity of their surfaces is interrogated. In reality, however, the two proteins are fluctuating; they are flexible. When they associate, there are often subtle conformational rearrangements in both proteins. We’ve been collaborating with a computational team at the Barcelona Supercomputing Facility regarding this. We reported earlier this year on a strategy to improve prediction of binding partners and docking modes between ubiquitin and several of its partners. The task of ubiquitin is to bind proteins. If you try to predict complexes with it you have to take into account the flexibility. We used NMR experiments to define a conformational ensemble for ubiquitin; this is a collection of all the conformations that have a certain probability of being populated by the protein. It’s multimodal, and when all the conformers are probed in the simulation, you get accurate complexes. The collection of conformers agrees with the experimental data better than the crystal structure. So protein flexibility, when accounted for by conformational ensembles, improves the performance of docking methods.

MP: What about the other side of the lab?
The other side of the lab is working on a project that also involves a question related to PPIs because it involves the association of a protein with itself. Flexibility often makes proteins more probable to aggregate and form plaques as a consequence of that flexibility. We are interested in this relationship: more flexibility – more aggregation, more flexibility – faster aggregation, different types of flexibility – different types of aggregates, these sorts of questions. But we were using a protein that is not particularly important to biomedicine.

MP: And then?
The story is quite funny, actually. Shortly after I had arrived at the IRB, while we were in the midst of the methods development project, my wife’s friend asked me to describe our research to her. The incident coincided with a real effort on our part to try and adapt our research to what we have here [at the IRB]. I realized that it would be attractive to get into a biomedical problem. Rather than working only on the methods for their own sake, we wanted to apply the methods to an important protein. I was explaining our research about aggregation to her when she said, “I have a family member that has a disease that is similar to this, it’s called Kennedy’s disease.” I looked up Kennedy’s disease on Wikipedia and found out it’s a rare familial genetic disease of which not much is known. But it had to do with aggregation of a protein called androgen receptor, a protein that is responsible for the male phenotype. In the cytosol it is in an inactive state and then upon binding testosterone large conformational changes occur. This leads to translocation into the nucleus and the protein then acts as a transcription factor to upregulate specific genes.

MP: Wow. So it was a project that was perfectly suited to your program, right?
Yes. Around that same time there was a call by Catalan funding agency that targeted rare diseases. So I quickly wrote up an application and got about 400.000 euros (shared with two other groups) to work on the androgen receptor aggregation project – [in order] to characterize how it aggregates, etc.

MP: Isn’t androgen receptor linked to prostate cancer too?
Yes, it is also the main target in prostate cancer. The normal state of prostate cells is to be turned “on” via testosterone through the androgen receptor. Unless there is constant activation by testosterone, the cells will go into apoptosis. So a common pharmacological treatment for prostate cancer is to stop the activation of androgen receptor. But in a certain fraction of patients that undergo this therapy, [after] two to three years, they stop responding to the treatment. This recurrence is called castration resistant prostate cancer. Here the receptor is able to activate itself even in the absence of testosterone. We’re trying to look into this process using our methods. The reason being that the protein sequences (via sequencing of the patients’ DNA) for the androgen receptors have mutations. They are all in a domain that is totally flexible, and there are many hints that this is the domain that drugs should really target. So crystallography can’t give much information here but our NMR methods can….and do, because we can look at these “intrinsically disordered” proteins.

MP: So it’s methods development to look at protein flexibility and its implications for aggregation and the application of the methods to therapeutically important proteins?
Yes, and the upside is that, if you look at the IRB website we have five research program areas: chemistry and molecular pharmacology, structural and computational biology, cell and developmental biology, oncology, and molecular medicine. Out of those five, three or four of the program areas are in this one project. These two projects related to androgen receptor – Kennedy’s disease and prostate cancer – have been well received by my colleagues and students.

MP: I haven’t asked about the IRB itself. How would you describe it?
For me, right now, the reasons I joined IRB were that I could solve two [problems]. It was here I knew I would “be where I belong.” I am from here and I have friends and I like to live here. And there was a place I could [perform] the type of research I wanted with the resources that I think are necessary. Because the two things happened in the same place, I took [the position]. It was very pragmatic.

(Image Source: Institute for Research in Biomedicine)

MP: What resources, maybe beyond the obvious instrumentation, etc.?
At the IRB, all the resources necessary to ask broad, impactful questions are provided. In return there is an expectation that investigators are ambitious about their science; big ideas are encouraged. By design, there is no process for tenure at the IRB, and investigators are reviewed every five years. This creates a certain urgency or an intensity that that defines the environment here. It is quite effective for motivating everyone.

MP: It sounds like Janelia Farm on the Diagonal.
Yes, it is a bit like Janelia Farm on the Diagonal. (La Diagonal is a huge boulevard in Barcelona where the IRB is located.) When I left to do a post-doc in Cambridge, I thought, “I am going to a great place in a very important group who try to solve huge fundamental problems. I will not be able to do this in Barcelona ever so I may as well enjoy it and if I do well I will look for positions elsewhere – in the US or the UK to run a research group.” And then, I realized it was possible to do it here in Barcelona at the IRB, so I applied to the job and I got it.

MP: What made this possible?
There is another virtual institution, called iCREA that hired me from Cambridge to work at the IRB; they gave me a salary for five years. Let me give you some background. Before I left for Cambridge, there were two places where you could do research: as a university professor or as a CSIC investigator. CSIC is a national research institute all across Spain – it’s similar to the CNRS in France – one institution devoted to many different types of research. But there was [an] interesting development in Cataluña around the time when I left [for Cambridge] in which the government decided that those two institutions were not appropriate for doing cutting edge, high impact research for many reasons – the rigidity of the hiring system, tenure – which can cause people to relax, bureaucracy, etc. etc. etc. Two instruments were created by the Catalan government to solve this problem. One is the creation of iCREA; it is a very small agency that recruits good scientists and negotiates a salary with them and assesses their performance every 3-5 years. This instrument is open to all institutions (universities, CSIC) as a way to support salaries for their staff. This was a way that many talented scientists have moved [back] to Barcelona. The big thing is that the selection of the iCREA researchers is done by committees of experts that couldn’t care less about anything except the quality of the science of the applicants. There was a huge emphasis on that. Each year there is a huge competition for 20 positions in iCREA. I was brought in to the IRB on a (now discontinued) junior iCREA program. In parallel to this was the creation of centers of excellence. The government created a number of research institutes of varying sizes in areas of science that were considered important to Cataluña. Of the many centers that were created, IRB is one of the biggest. They are totally different than a university or CSIC – more intensity, more resources. Both university faculty and CSIC researchers can be investigators at an institute along with iCREA researchers… or in fact “no ones” – investigators that are sponsored directly by the institute. We have all of these varieties at IRB. These two instruments have been very successful, so successful that the competition is quite intense. They have changed the panorama completely – now we have in Cataluña research centers that are top quality in Europe, top quality in the world.

There’s something about this neighborhood of Barcelona that encompasses Camp Nou and the IRB. The motto of Barça is visible from an arial view of the stadium, “Més que un club (More than a club).” Perhaps the same can be said for the IRB, “Més que un institut.”

Image from Google Maps. A indicates the Institute for Research in Biomedicine.

*Name: Xavier Salvatella
Position: Investigator at the Institute for Research in Biomedicine (IRB) in Barcelona.
Research: Characterizing the flexibility of proteins and the implications of this flexibility for biology
Important: Married, father of son Lluc (2 years) and daughter Maria (4 months)
Why Barcelona? I am from here and I have friends [here] and I like to live here
Why IRB? And [in Barcelona] there was a place I could [do] the type of research I wanted [and] where there [were] resources that I think are necessary [for that research]. Because the two things happened in the same place, I took [the position]. It was very pragmatic.
Quirky: [I have] a peculiar fascination with pens and personal office supplies.

This entry was posted in Uncategorized. Bookmark the permalink.

39 Responses to Interview with Xavier Salvatella – by Mark Peczuh

  1. I visited many web sites except the audio quality for audio songs
    existing at this web site is in fact marvelous.

    Also visit my web site dominos pizza vouchers online

  2. mobile games says:

    Write more, thats all I have to say. Literally, it seems as though you relied on the video to make your point.

    You definitely know what youre talking about, why
    throw away your intelligence on just posting videos to your
    site when you could be giving us something informative to read?

  3. Hi there! This is kind of off topic but I need some advice
    from an established blog. Is it hard to set up your own blog?
    I’m not very techincal but I can figure things out pretty quick.
    I’m thinking about making my own but I’m not sure where to begin.
    Do you have any tips or suggestions? Thank you

    Feel free to surf to my web blog telecharger subway surfers

  4. Stacia says:

    I visit each day a few websites and blogs to read content, except this website offers feature based content.

    Feel free to visit my web blog :: telecharger pdf creator (Stacia)

  5. Whats up are using WordPress for your site platform?

    I’m new to the blog world but I’m trying to get started and create my
    own. Do you require any coding expertise to make your
    own blog? Any help would be really appreciated!

    Feel free to visit my page: game of thrones season 4

  6. Anonymous says:

    Hello. Have you any idea learning to make an internet site mobile friendly?
    I’m looking for a style or wordpress tool that could possibly take care of this matter. If you have any suggestions, please share.
    Rapid problem that’s completely away issue.
    My web-site seems to be peculiar when surfing.

  7. dog training says:

    If you try to do too much, the puppy will probably not remember much
    except that it was an unpleasant experience, and that will make
    it more difficult when the time comes for the next training
    session. Some of the things I learned in general by watching this DVD
    series are that 95 per cent of dogs who are lying down bark less because they are more
    relaxed and that it takes dogs an average of 45 seconds to figure out what their owners
    want. Its HVAC technician program costs, as of 2013, a total of $899 (with a $200 rebate offered at
    this writing) and covers basic cooling technology, refrigerant charging,
    commercial refrigeration and heating, and also domestic appliances.

  8. antalya escort says:

    Escort Bayan Artık Hayal Değil Özel hayatınızdaki en iyi kararı vermek üzeresiniz. antalya escort bayan hizmetimizden yararlanarak gündelik hayatın antalya escort ilan

  9. antalya movies says:

    Elsewhere in neighboring Iraq, Islamic State of Iraq and the Levant (ISIL) fighters attacked a riverside town north of antalya movies Baghdad with gunboats and a car bomb, killing 17 people and wounding 54, a security source said.

  10. I had Facebook and just deactivated, FB wasn’t for me…I always
    tend to succeed in out on a regular basis and if I don’t, no one put up anything in my wall or there is no interaction with me in any respect…at all times is about commenting in regards to
    the Put up..just acquired tired of it..moreover I should be productive
    in different areas of my life..people at all times must say something about, politics, travels, family….so whatever..I believe I
    really feel more at peace and go old fashioned…much much better!!!

  11. When attempting to focus on internet affiliate marketing, you should
    try to make an e-book to generate on document sharing sites.

  12. You should take part in a contest for one of the finest blogs on the net.
    I’m going to recommend this site!

    Feel free to surf to my site: compagnie Demenagement Martin

  13. whoah this weblog is excellent i really like reading your posts.

    Stay up the great work! You understand, a lot of persons are searching round for this info, you could help them greatly.

    Feel free to surf to my homepage … demenagement martin

  14. Get in touch with bloggers: Approach individual bloggers that are aligned
    together with your product and market and also have if they
    would end up being considering being an affiliate.

  15. model eskortlar says:

    Bir adam bir kız model dedi sonra:. “Aşk, bir gökkuşağı gibi rengarenk ve insanlar gülümseme yapar Aşk bir okyanus gibi, bu derin ve güzel Aşk güneş gibidir, parlar ve sıcak

  16. Don’t change it out too frequently since it is what your
    fans will keep company with your brand, highlighting your
    posts within their news feed therefore.

  17. Anonymous says:

    I really love your blog. This post was interesting. I really enjoyed it!
    Keep up the good work. A++++ THUMBS UP!

  18. In fact, the single glass reactor is the most important on of all glass reactors that may include many different types such as double layer reactor, and see here:, finner layer reactor, chemical reactor or other types of reactors.

  19. Thank you for sharing the article. It’s very cool. Hope to hear more from you.

  20. Fine way of explaining, and fastidious paragraph to obtain facts regarding my presentation subject, which i am
    going to deliver in university.

  21. It’s amazing in favor of me to have a website, which is helpful in support of my experience.

    thanks admin

  22. Hi my family member! I want to say that this article
    is amazing, nice written and come with almost alll important infos.

    I’d like to see extra posts lioe this .

  23. Jack says:

    And forget a DIY stunt because chances are you are not going to read the
    manual first. There are many casino websites all over the internet that offer mobile
    casino bonus for the gambler who is busy and wants to be posted about the
    offers regularly. Joan: But recently I made a very pleasant observation.

  24. Rhonda says:

    Hence, you should opt for a balance of quality hosting services and affordable
    costs. We have dedicated customer service executives, who are always here to help you
    with required information. Web page hosting is in general adequate
    only for personal home pages.

    Feel free to visit my blog To get more information on website hosting drop a line for us here.

  25. Norris says:

    Make sure the quote includes the subsequent: origin (shipper’s door or port), destination (consignee’s door, port or unloading
    warehouse). The popular NCIS spin-off television series returns in NCIS: Los Angeles: The Complete Fourth Season.
    It’s crucial that when somebody realized the requirement
    for you his car, she must start gaining car shipping quotes as soon as they can.

  26. Paulette says:

    Every weekend i used to pay a visit this site, as i wish for enjoyment, for the reason that this this site conations
    genuinely gopd funny data too.

  27. Hi there it’s me, I am also visiting this site on a regular
    basis, this site is truly fastidious and the visitors are genuinely sharing pleasant thoughts.

  28. Dale says:

    Couponing ideas: if you’re a person while in the same
    store you view to the display, there’s a superb chance you’ll never be able to have the
    bargains profiled.

  29. Niki Kruzel says:

    Hey, regarding Clickbank – do you have ideas about improving sales on a non-niche website? I have a document sharing website and as such it is extremely to match products to the visitor. regards

  30. hello there and thank you for your information – I have certainly picked
    up anything new from right here. I did however expertise some technical issues using this web site, since I experienced to reload the web site many times previous to I could get it to load
    properly. I had been wondering if your hosting is OK?

    Not that I am complaining, but sluggish loading instances times
    will sometimes affect your placement in google and can
    damage your quality score if ads and marketing with
    Adwords. Well I’m adding this RSS to my e-mail and could look out for a lot
    more of your respective exciting content. Make sure you update this
    again very soon.

  31. says:

    Your User ID is assigned to you personally when you join….
    When you subscribe to a hotmail messagerie ( account, there are several ways to customize it.

  32. Lazaro says:

    Very shortly this site will bbe famous amid all blogging users,
    due to it’s pleasant posts

  33. my aol email says:

    Checking your my aol email over a cell phone
    makes it simple for people to remain in touch when not at their computer stations.

  34. Aretha says:

    Nice post. I used to be checking constantly this blog
    and I’m inspired! Extremely helpful information specially the closing section :) I care for such information much.
    I used to bbe seeking this particular info for a very long time.
    Thank youu and good luck.

  35. Everyone loves what you guys are usually up too.
    This kind of clever work and exposure! Keep up
    the terrific works guys I’ve you guys to my blogroll.

    My my website: netflix customer service phone number

  36. Keep on writing, great job!

    My my site: amazon smile login

  37. example says:

    I am in fact grateful to the owner of this site who has shared this impressive paragraph at
    at this time.

  38. Speculations and loans in foreign fields are likely to bring us into war… The war-for-profit group has counterfeited patriotism.

  39. how exactly is fo4 a step up from this? because you can choose a faction? because the game is forcing you to be a good guy from the very beginning, was a huge disappointment when i found out i couldn’t kill preston and co, and couldn’t even decline their quest to make a bad guy playthrough as i had actually

Leave a Reply

Your email address will not be published.

You may use these HTML tags and attributes: <a href="" title=""> <abbr title=""> <acronym title=""> <b> <blockquote cite=""> <cite> <code> <del datetime=""> <em> <i> <q cite=""> <strike> <strong>