Tag Archive | PRBB

Science at PRBB: Roberto Elosua’s group on cardiovascular epidemiology and genetics

The Cardiovascular epidemiology and genetics research group, led by Roberto Elosua and Jaume Marrugat at the IMIM, tries to identify the incidence of cardiovascular diseases, their determinants and evaluate prevention strategies. In this short video, Dr Elosua explains their research more in detail.

Therapeutic virus-like particle- based vaccines against cervical cancer

Cervical cancer represents the second most frequent gynecological malignancy in the world. It is caused by a persistent virus infection by the high-risk human papillomavirus (HR-HPV) but no cervical cancer vaccine has been marketed to date. In a paper published in PLoS, Juan Martin Caballero, director of the PRBB animal facility, together with colleagues from a pharmaceutical company have generated a virus-like particle (VLP)-based vaccine to treat this cancer and have tested it in humanized transgenic mice.

The researchers took a long C-terminal fragment of the HPV-16 E7 protein – one of the two viral proteins necessary for induction and maintenance of malignant transformation – and introduced it into the infectious bursal disease virus (IBDV) VLP. The combination of tumor antigens and IBDV-VLPs has been shown as a good strategy to boost the immune response and direct it against different types of cancer.

The authors tested the therapeutic potential of their new vaccine, VLP-E7, in HLA-A2 humanized transgenic mice grafted with TC1/A2 tumor cells. They performed a series of tumour challenge experiments demonstrating a strong immune response against already formed tumors, including its complete eradication. Remarkably, therapeutic efficacy was obtained with a single dose without adjuvant and it persisted when the mice were re-challenged with a second tumor cell inoculation. As the authors state, this indicates a high immunogenic potential and in vivo efficacy of  their cervical cancer candidate vaccine, VLP-E7, although further studies will be necessary to investigate the potential of the IBDV VLP carrier and its applications to other human diseases.

Reference:

Martin Caballero J, Garzón A, González-Cintado L, Kowalczyk W, Jimenez Torres I, Calderita G, Rodriguez M, Gondar V, Bernal JJ, Ardavín C, Andreu D, Zürcher T, von Kobbe C. Chimeric Infectious Bursal Disease Virus-Like Particles as Potent Vaccines for Eradication of Established HPV-16 E7-Dependent Tumors. PLoS One. 2012;7(12):e52976

Challenges and limitations of Bioinformatics: XI Bioinformatics Symposium at the PRBB

More than 225 people registered to the XI Bioinformatics Symposium, co-organised by the Spanish Institute of Bioinformatics (INB) and the Portuguese Bioinformatics Network and hosted by the PRBB. From yesterday, January 23 and until tomorrow, Jan 25 they will enjoy the talks of three keynote speakers and another 31 scientists, as well as more than 100 scientific posters.

Alfonso Valencia, director of the INB – and who had recently been at the PRBB for another bioinformatics meeting – explained at the inauguration that the aim of the conference, organized jointly with the Portuguese community for the last three years, was to stimulate collaborations between both countries and to grow as a community, something that seemed to have been achieved as evidenced by the record audience.

The event hosted a student symposium in the first morning, and a discussion session in the afternoon on the challenges and limitations for bioinformatics researchers.  One of the issues raised in this round table was how to deal with the large amounts of data that are being gathered, and Ana Rojas (IMPPC) mentioned that a centralized repository of all the data would be a good thing, but that funding is necessary –and nowadays very difficult to get! Another issue related to the sheer amount of data is the need for more computer power and in that sense a call was sent from the Barcelona Supercomputing Centre to all scientists to make more use of the existing supercomputers in Europe.

Challenges of another nature were also discussed. Bioinformatics is an interdisciplinary area by nature. Its three pillars are molecular biology, mathematics/statistics/physics, and computer science/engineering. The difficulty of finding researchers that are trained in all three areas is large, but one of the speakers also mentioned the difficulties that those well-trained researchers meet during their career development.  A biologist doesn’t fit very well in a Computer Science department, nor an engineer in the Biology department. And the Impact Factor of the computer science journals is much lower than those of biology, so when fighting for a competitive position, computer scientists would always be in disadvantage…  all in all, everyone agreed that sooner or later, every experimental group will need to have a bioinformatics expert with them – or at least someone with a basic knowledge of data analysis who can speak ‘bioinformaticians’ language.

The XI Bioinformatics Symposium continues today and tomorrow – you can follow it in twitter at #jbi2012.

Report by Maruxa Martinez, Scientific Editor at the PRBB

The PRBB consolidates its internationalization

Take a look at the new issue of Ellipse, the monthly bilingual publication of the PRBB. We have now reached 50 editions!!!!

Check out how the demography of the PRBB has changed over the last 5 years, to reach 50 different nationalities amongst our 1,345 residents. Actually, currently 41% of the researchers at the park are non-Spanish!

How does the biological clock controls skin stem cell activation? And did you know the ‘out-of-Africa’ route was through Arabia, and not Egypt? CRG researchers show how it is possible to predict the phenotype from individual genomes; an international group of scientists ask for more ethical communication of the results of epidemiological studies involving molecular or genetic risk factors; the CRG celebrates its X symposium about computational biology; and researchers at IMIM discover a new reprogramming mechanism for tumour cells. Don’t miss Joan Benach (UPF)’s group profile about research on health inequalities, “the greatest current epidemic”, and Josep Ma Antó (CREAL) talking about his career.

Enjoy!

How does genotype determine phenotype?

Very interesting talk by Edward Marcotte today at the PRBB!

He is an expert in proteomics, but touches all aspects of systems biology, and today he asked the following question: how does genotype determine phenotype? Can we predict the outcome of all the genomic variation we are uncovering with the many genomic projects we are doing nowadays?

Well, his lab is certainly trying to do so, and using three different strategies which I will summarise very briefly:

1.  Using functional gene networks, which are based on data such as mRNA expression, protein-protein interactions (PPI), etc. These networks presumably are formed by genes that are involved in the same biological processes. From here one only needs to follow the “guilt-by-assotiation” principle and assume that, if a gene in that network is involved in a particular phenotype (a disease, for example), the genes around it might also be so. They have tested this in yeast, C.elegans, Arabidopsis, rice and mouse, at least. They have managed to validate predictions for up to 200 genes. And they have come up with a valuable principle: that phenotypes reflect biological modules, rather than single proteins. That is, it is not a specific proteins that is essential, but a specific complex.

protein interaction networks

2. A systematic mapping of stable protein complexes in humans, which they have done in collaboration with labs in Toronto and which includes more than 2000 Mass spec experiments. From here they have inferred more than 600 stable complexes in humans (more than 500 of them with more than 3 components), of which 1/3 are unknown. Now the idea is to use this PPI network as a framework for linking genes to diseases. And they are doing so with one children developmental disease, the Cornelia de Lange syndrome, for which 3 known genes explain only the 50% of cases. They have selected some of the proteins which are around those three in the network and are currently sequencing them in patients.

3. Using model organisms to infer human disease genes. This is by far the one that I was most surprised about. It turns out that looking for what he called phenologs (orthologous phenotypes between organisms, for example, which yeast phenotype is equivalent to breast cancer in humans) one can find surprising disease models. For example, yeast sensitivity to lovastatin is a model for angiogenesis defects in humans! This is found looking for the yeast orthologous  of human genes involved in angiogenesis, and checking which phenotype those yeast genes are involved in. Then one can look at the rest of the yeast genes involved in that phenotype, and check if their human orthologous might be involved in angiogenesis.

And then, in principle, one could even use screening in yeast to find angiogenesis inhibitors. And the surprising thing is that it works! The Marcotte lab is actually about to start a phase I clinical trial on a drug they found this way and which they hope might be useful for glioblastoma. This is just one example, but according to him, this ‘phenologs’ strategy seems to work for more than 50% of the human genetic diseases… One big lesson that stems from this knowledge is that protein modules are conserved through evolution even if the phenotype is not – a concept he called ‘evolutionary repurposing’. Very interesting indeed.

Report by Maruxa Martinez, Scientific Editor at the PRBB

XIth Spanish Symposium on Bioinformatics 2012

If you are interested in Computational Biology, don’t miss this upcoming conference at the PRBB!! It will take place in January 23-25 and the deadline for registration is November 30, 2011.

Follow it in twitter!!!!!

#jbi2012

“Insights from proteomics into cellular evolution and surprising disease models”

Don’t miss Edward Marcotte‘s talk next week at the PRBB!!

Coming from the Institute for Cellular and Molecular Biology (ICMB) at the University of Texas at Austin, USA, Marcotte will give a talk entitled “Insights from proteomics into cellular evolution and surprising disease models” next Tuesday November 22 in room 473.10 at 12h.

He has been invited by Gian Gaetano Tartaglia (CRG).
Marcotte works in systems and synthetic biology, studying the large-scale organization of proteins. He tries to reconstruct the ‘wiring diagrams’ of cells, learning how all proteins are associated into pathways, systems, and networks. He is interested both in discovering the functions of the proteins and in learning their underlying organizational principles. For that he uses both computation, and experimentation, especially high-throughput functional genomics and proteomics approaches.

How to integrate your experimental data in a nice image

SVGmap is a configurable image browser for experimental data, a  new tool developed by the biomedical genomics group of the GRIB (UPF-IMIM) at the PRBB. According to the group “it is useful to create browsers for individualized high-quality images which change the color of some regions according to some values”.  It has recently been published in Bioinformatics.

You can read more about it at Núria López-Bigas’ laboratory blog: http://bg.upf.edu/blog/

CRG Symposium “Computational Biology of Molecular sequences”, part 3

On the second day of the conference, some more interesting talks at the “Computational Biology of Molecular sequences” X CRG Symposium taking place at the PRBB Conference Hall. I will focus on one talk of each of the sessions (genome regulation, RNA analysis and genome annotation), although all were very interesting!

Ron Shamir (Tel Aviv University) presented Amadeus, a software platform for genome-scale detection of known and novel motifs in DNA sequences, and explained some of the findings they have done with it. He also presented his new book “Bioinformatics for biologists”, which will surely be very useful for many biologists drowning in today’s sea of data and tools for analysing it.

Anna Tramontano (Sapienza University), the only female out of the 20 invited speakers and a very well-known figure in the protein world, gave her first RNA talk ever, as she presented it. She talked about a new method for controlling gene expression: a long ncRNA which contains 2 miRNAs within its sequence, and which competes with those miRNAs on binding to their target genes.

Tim Hubbard (Sanger Institute) gave so much information in 45 min that was hard to keep track of it all. He started with the catch 22 of reference genomes: we want it to be complete, but we don’t want it to change… the proposed solution: to keep the reference genome and to release patches with ‘novel’ information or with corrections (the ‘fix’ patches) whenever we get more information. Now, this means that alignment algorithms will need to be aware of patches, he warned the audience.

He then moved on to the costs of sequencing a human genome (5000 pounds, as per October 2011) and said that every 2-4 years the cost drops by 10 times! With this ever-lowing costs, he said, in the UK there has been quite a lot of movement regarding future policies on genomic medicine. And the main question is: what is the health economic value on having all this information, of sequencing the whole population? Nobody knows that yet, but according to Hubbard, one day the cost of sequencing will go low enough and the usefulness of the information will grow enough so that they will both meet and make it viable.

He finally presented the ITFoM (IT Future of medicine) project, one of the six funded by the Future and Emerging Technologies (FET) flagship programme of the EU – which has the goal of “encouraging visionary, “mission-oriented” research with the potential to deliver breakthroughs in information technology with major benefits for European society and industry”. The ITFoM project is expected to run for at least 10 years and will receive funding of up to € 100 million per year.  Considering what they aim to do – integrating all available biological data to construct computational models of the biological processes that occur in every individual human – they will certainly need that much money… Just consider this fact: to cover all the ‘cancer genomes’ appearing every day, we would need to sequence a new genome every 2 seconds!

So, that was my own pick of the day. Of course, much more happened at the meeting. You can find summaries of all talks and much more at the Symposium’s website http://2011symposium.crg.es/

And if you are interested in Computational Biology, don’t miss two upcoming events also at the PRBB:

Report by Maruxa Martinez, Scientific Editor at the PRBB

CRG Symposium “Computational Biology of Molecular sequences”, part 2

In the early afternoon, genome evolution was still the focus of the talks at the X CRG Annual Symposium. Why do we care about reconstructing ancestral genomes? Apart from the fact that it’s difficult and fun (reasons enough for most computer scientists), according to Mathieu Blanchette (McGill University) it can help us to study the mechanisms of genome evolution and also for the identification of functional regions, such as TFBS. Blanchette also showed how to turn multiple sequence realignment into a game with Phylo http://phylo.cs.mcgill.ca/

Following on into genome regulation, Philipp Bucher (Swiss Institute of Bioinformatics) explained the workings of the Chip-seq technology and talked about the computational promoter analysis in the era of ultra-high-throughput sequencing. And to finish off the quite long day, Alfonso Valencia (CNIO) substituted Gene Myers (Janelia Farm), who regretfully couldn’t make it at the last minute. Valencia talked about open questions in the protein universe, such as: what proteins are in a cell? What protein complexes exist? How did protein families originated? And are we using the right tools and approaches to analyze pathways? Some may think that we know the answers to some of them, but Valencia showed otherwise…

More tomorrow! You can also check the rest of the program here.

 

Report by Maruxa Martinez, Scientific Editor at the PRBB

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