IRB Barcelona - NEWS

Researchers discover a new family of key mitochondrial proteins for the function and viability ...

irbbarcelona.org — Wed, 09 May 2012 12:00:00 +0100

This family comprises a cluster of six genes that may be altered in neurological conditions, such as Parkinson’s and Charcot-Marie-Tooth disease

A team headed by Eduardo Soriano at the Institute for Research in Biomedicine (IRB Barcelona) has published a study in Nature Communications describing a new family of six genes whose function regulates the movement and position of mitochondria in neurons. Many neurological conditions, including Parkinson’s and various types of Charcot-Marie-Tooth disease, are caused by alterations of genes that control mitochondrial transport, a process that provides the energy required for cell function.

“We have identified a set of new genes that are highly expressed in the nervous system and have a specific function in a biological process that is crucial for the activity and viability of the nervous system”, explains Eduardo Soriano, head of the Neurobiology and Cell Regeneration group at IRB Barcelona and full professor at the University of Barcelona (UB).

By means of comparative genomic analyses, the scientists have discovered that these genes are found only in more evolved mammals, the so-called Eutharia, these characterized by internal fertilization and development. “This finding indicates the relevance of mitochondrial biology. When the brain evolved in size, function and structure, the mitochondrial transport process also became more complex and probably required additional regulatory mechanisms”, says Soriano. "Likewise, given the origin of the gene cluster, in the transition between primitive mammals, such as marsupials (kangaroos) and the remaining placental mammals, it is tempting to propose that the cluster is linked to the increased complexity of the cerebral cortex in the lineage that leads to humans", adds the full UB professor Jordi Garcia-Fernàndez, collaborator in the study.

Correct brain function is highly energy-demanding. However, this energy must be finely distributed throughout neurons —cells that have ramifications that can reach up to tens of centimetres in length, from the brain to the limbs. This cluster of genes forms part of the “wheel” machinery of mitochondria and regulates the localization of each cell on the basis of its energy requirements. “These genes would be like an extra control in cellular mitochondrial trafficking and they interact with the major proteins associated with the regulation of mitochondrial transport”, explains Soriano.

Another striking characteristic of these new proteins is that they are found both in mitochondria, the function of which has already been described, and in the cell nucleus, where their function is unknown. “They may also be involved in the regulation of gene expression, a possibility that we are now studying”. In addition to their potential involvement in brain pathologies, the researchers believe that these proteins may be related to metabolic diseases and cancer.

This study has been performed in collaboration with the teams headed by Jordi Garcia-Fernàndez, from the UB, Ramón Trullás and Javier García-Sancho, both from the CSIC, and Antoni L. Andreu, from the Hospital de la Vall d´Hebron.

Reference article:

The Eutherian Armcx genes regulate mitochondrial trafficking in neurons and interact with Miro and Trak2.

G López-Doménech, R Serrat, S Mirra, S D’Aniello, I Somorjai, A Abad, N Vitureira, E García-Arumí, MT Alonso, M Rodriguez-Prados, F Burgaya, A L. Andreu, J García-Sancho, R Trullas, J Garcia-Fernàndez and Eduardo Soriano.

Nature Communications (2012): DOI number: 10.1038/ncomms1829

Ra�l M�ndez elected EMBO member

irbbarcelona.org — Wed, 09 May 2012 12:00:00 +0100

Fifty-five leading life scientists from Europe and around the world were recognized today by EMBO for their excellence in research

IRB Barcelona /ICREA researcher, Raúl Méndez, has been recognized by EMBO for his excellence in research. Today EMBO welcomed 55 new members, 48 of who are from Europe and neighboring countries while seven scientists from Argentina, Australia, South Korea and the United States have joined as Associate Members. In total, EMBO membership now comprises almost 1,550 life scientists in the international scientific community. (read more in EMBO website)

Raúl Méndez, principal investigator of the Translational Control of Cell Cycle and Differentiation laboratory, said that “this is recognition is very much appreciated and I hope it opens up opportunities to work with groups involved in distinct fields of molecular biology to mine”.

One of Méndez’s current priorities is the study of the relation between the processes that control protein production and several diseases, such as cancer. “Alterations in the translational control of mRNAs cause tumour expansion, and therefore their study is critical in order to understand cancer and to develop new therapies”. For this purpose, this researcher combines studies using the frog Xenopus Laevis, a highly useful animal model in biomedicine, with other studies in mice and human cells.

Among his publications, special mention is given to work published in prestigious journals such as Nature, Cell and Nature Cell Biology in 2008, in which he showed the exquisite temporal and spatial intracellular regulation of mRNAs, and in Nature Cell Biology in 2010, where he reported for the first time that these regulatory mechanisms occur not only during embryonic development but also in adult cells. In 2011, he described in Nature Medicine a new reprogramming mechanism for the expression of genes responsible for turning a healthy cell into a tumor cell, in an study in collaboration with the IMIM-Institut de Recerca Hospital del Mar.

An international authority in gene regulation

Raúl Méndez obtained his PhD from the “Centro de Biología Molecular 'Severo Ochoa'” in Madrid in 1993. He then moved to the U.S., where he did post-doctoral work at the Louisiana State University Medical Center and at the University of Massachusetts. In 2001 he returned to Spain to take up a post as group leader in the Center for Genomic Regulation, where he remained until joining IRB Barcelona in January 2011.

The extensive research performed by Méndez has earned him several awards, including the prestigious “2010 Carmen y Severo Ochoa Award for Research” and the “2008 Ciutat de Barcelona Award” for research. He is currently involved in several European projects, among which special mention is given to that granted by the Association for International Cancer Research for the study of mRNAs in the context of pancreatic cancer.

Embo Press Release (PDF)

Glycogen accumulation in neurons causes brain damage and shortens the lives of flies and mice

irbbarcelona.org — Wed, 02 May 2012 12:00:00 +0100

Work by IRB Barcelona researchers will further the study of neurodegenerative diseases such as Lafora progressive myoclonic epilepsy

Collaborative research by groups headed by scientists Joan J. Guinovart and Marco Milán at the Institute for Research in Biomedicine (IRB Barcelona) has revealed conclusive evidence about the harmful effects of the accumulation of glucose chains (glycogen) in fly and mouse neurons. These two animal models will allow scientists to address the genes involved in this harmful process and to find pharmacological solutions that allow disintegration of the accumulations or limitation of glycogen production. Advances in this direction would make a significant contribution to investigation into Lafora progressive myoclonic epilepsy and other neurodegenerative diseases characterized by glycogen accumulation in neurons. The journal EMBO Molecular Medicine publishes the results of the study this week.

“Our data clearly indicate that glycogen accumulation alone kills neurons and thus dramatically reduces lifespan”, explains Guinovart, an expert in glycogen metabolism, group leader at IRB Barcelona, and senior professor at the University of Barcelona, “because the only thing we have manipulated in the neurons is their capacity to produce glycogen”.

The inclusion of the Drosophila fly in the study provides in vivo confirmation of the theory in another animal model as these flies also show the same symptoms of degeneration as mice when glycogen accumulates in neurons. However, in addition the use of Drosophila will speed up obtaining genetic data and the screening of therapeutic molecules. “In a short time we will be able to perform a massive search for genes involved in the pathological process and to understand it better at the molecular level”, emphasizes Marco Milán, ICREA researcher at IRB Barcelona and a specialist in Drosophila. “But the flies will also be useful to identify pharmacological molecules that can cure”, he explains.

The IRB Barcelona teams are designing several experiments to identify the possible therapeutic targets that may be useful to prevent glycogen accumulation in neurons. In addition to the direct relation to Lafora epilepsy, a progressive degenerative disease that affects adolescents and has no cure, glycogen accumulation could be the main cause of other neurodegenerative illnesses such as Adult polyglucosan body disease and Andersen’s disease.

Reference article:

Deleterious effects of neural accumulation of glycogen in flies and mice

Jordi Duran, María Florencia Tevy, Mar García-Rocha, Joaquim Calbó, Marco Milán, Joan J. Guinovart.

EMBO Molecular Medicine (2012). Doi: 10.1002/emmm.201200241

What does European science need to flourish?

irbbarcelona.org — Fri, 27 Apr 2012 12:00:00 +0100

On May 3-4, the European science policy lobby group the Initiative for Science in Europe (ISE), with the support of the Institute for Research in Biomedicine (IRB Barcelona), the Ramon Areces Foundation and the Government of Catalonia, will hold its annual conference at the Institute for Catalan Studies in Barcelona.

Under the title of “Strengthening the European Research Area: What Does Science Need to Flourish?”, the ISE will bring together key players in europe to discuss aspects such as how to involve of scientists in the governance of the European Research Area (ERA) and how to organise cross-border research collaboration.

Helga Nowotny, president of the European Research Council (ERC), Iain Mattaj, director general of the European Molecular Biology Laboratory (EMBL), Pär Omling, president of the European Science Foundation, Telemachos Telemachou, Science Counselor of Cyprus, and Octavi Quintana Trias, Director of the EC's European Research Area (ERA) are among the speakers invited to the event which will welcome up to 150 participants. The Secretary for Research and Universities of the Government of Catalonia, Antoni Castellà, will participate in the inaugural act, and the Minister of Economy and Knowledge of the Government of Catalonia, Andreu Mas-Colell, will participate in the conclusions.

ISE Conference programme: Strengthening the European Research Area: What does science need to flourish? (PDF)

ISE Conference website

ISE website