PROGRAMA GULBENKIAN INCENTIVA INVESTIGAÇÃO DE FRONTEIRA EM CIÊNCIAS DA VIDA

PROGRAMA GULBENKIAN INCENTIVA INVESTIGAÇÃO DE FRONTEIRA EM CIÊNCIAS DA VIDA

O Programa Gulbenkian de Apoio à Investigação na Fronteira das Ciências da Vida vai financiar com 50 mil euros dois projectos nesta área. O Júri do prémio elegeu a proposta de investigação de Hélder Maiato, do Instituto de Biologia Molecular e Celular, no Porto, e de Tiago Fleming Outeiro, do Instituto de Medicina Molecular, em Lisboa.

Este programa tem como objectivo apoiar a originalidade e o desenvolvimento de novas ideias criativas no trabalho de investigação nas ciências da vida (cutting-edge research). Resultou da vontade de induzir nos centros de excelência a capacidade de apostar e arriscar nos investigadores mais jovens, em áreas de fronteira.

Hélder Maiato vai analisar a “Aplicação de microscopia de fluorescência de partículas (speckles) e microcirurgia laser para o estudo dos mecanismos de produção de força responsáveis pelo movimento dos cromossomas”. O investigador principal no Instituto de Biologia Molecular e Celular no Porto quer compreender como é que determinadas estruturas e moléculas contribuem para os mecanismos de geração de força responsáveis pelo movimento dos cromossomas durante a divisão celular. A correcta distribuição dos cromossomas entre duas células que se dividem é um requisito absolutamente necessário para a vida, e falhas neste processo estão na base de várias anomalias congénitas, como o síndrome de Down (trissomia 21). Estas falhas são também características de vários tipos de cancro em humanos.

Hélder Maiato, doutorou-se em 2003 no Instituto de Ciências Biomédicas Abel Salazar, da Universidade do Porto.

Tiago Fleming Outeiro, investigador principal no Instituto de Medicina Molecular em Lisboa, investigará “O Envolvimento Molecular da Proteina DJ-1 na Etiologia da Doença de Parkinson”. O cientista vai procurar a etiologia da perda neuronal selectiva que causa a doença, nomeadamente estudando a proteína DJ-1, codificada pelo gene PARK7. A função normal da DJ-1 é ainda desconhecida, mas pensa-se que o seu envolvimento na doença se deva a defeitos na sua função normal, causados por mutações. Um trabalho que poderá permitir a identificação de novas vias envolvidas na Doença de Parkinson, e assim contribuir para o desenvolvimento de novas terapêuticas para doenças neurodegenerativas.

Tiago Fleming Outeiro doutorou-se em 2004 no Whitehead Institute for Biomedical Research, MIT, Cambridge, EUA.

PENS Summer School 2007

July 8-15, 2007 - Ofir, Portugal
PENS Summer School 2007
Novel Molecular Strategies to treat Neurodegenerative Diseases http://fens.mdc-berlin.de/pens/2007/schools/ofir/

Application Deadline: April 15, 2007

a-synuclein oligomers visualized by FLIM

Detection of novel intracellular a-synuclein oligomeric species by fluorescence lifetime imaging
Jochen Klucken^*,, Tiago F. Outeiro^*, Paul Nguyen^*, Pamela J. McLean^*,1 and Bradley T. Hyman^*
MassGeneral Institute for Neurodegenerative Disease, Alzheimer’s Disease Research Unit, Massachusetts General Hospital, Charlestown, Massachusetts, USA;
Department of Neurology, University of Regensburg, Regensburg, Germany

¹Correspondence: MassGeneral Institute for Neurodegenerative Disease, Alzheimer’s Disease Research Unit, Massachusetts General Hospital, 114 16^th St., Charlestown, MA 02129 USA

Oligomerization and aggregation of a-synuclein molecules are believed to play a major role in neuronal dysfunction and loss in Parkinson’s disease (PD) and dementia with Lewy bodies. However, a-synuclein oligomerization and aggregation have been detected only indirectly in cells using detergent extraction methods. Here, we show for the first time intracellular a-synuclein oligomerization using fluorescence lifetime imaging (FLIM). Two forms of a-synuclein homomeric interactions were detected: an antiparallel amino terminus-carboxyl terminus interaction between a-synuclein molecules, and a close amino terminus-carboxy terminus interaction within single a-synuclein molecules. Coexpression of the chaperone protein Hsp70, which can block a-synuclein toxicity in several systems, causes a-synuclein to adopt a different, open conformation, but Hsp70 does not alter a-synuclein–a-synuclein interactions. Thus, the neuroprotective effect of Hsp70 can be explained by its chaperone activity on a-synuclein molecules, rather than alteration of a-synuclein–a-synuclein interactions.

in FASEB J. 2006 Oct;20(12):2050-7.

The Power of Yeast

The high degree of conservation of cellular and molecular processes between the budding yeast Saccharomyces cerevisiae and higher eukaryotes have made it a valuable system for numerous studies of the basic mechanisms behind devastating illnesses such as cancer, infectious diseases, and neurodegenerative disorders. Several studies in yeast have already contributed to our basic understanding of cellular dysfunction in both Huntington’s disease and in Parkinson’s disease. Functional genomics approaches currently being undertaken in yeast will likely lead to novel insights into the genes and pathways that modulate neuronal cell dysfunction and death in these devastating diseases. In addition, the budding yeast constitutes a valuable system for identification of new drug targets, both via target-based and non-target-based drug screening. Importantly, yeast can be used as a cellular platform to analyze the cellular effects of candidate compounds, which is critical information for the development of effective therapeutics. While the molecular mechanisms that underlie neurodegeneration will ultimately have to be tested in neuronal and animal models, there are several distinct advantages to using simple model organisms to elucidate fundamental aspects of protein aggregation, amyloid toxicity, and cellular dysfunction.

Symposium at the 2006 FENS Forum

Together with Ana Cristina Rego, from the Center for Neuroscience and Cell Biology at the University of Coimbra, I am organizing a Symposium on "CAG Triplet Repeat Disorders".

This Symposium will focus in the polyglutamine diseases, with particular emphasis on Huntington’s disease (HD). The CAG repeat diseases include HD, spinocerebellar ataxias (SCAs) and other rare diseases. Mutations consisting of CAG expansions within the coding regions result in abnormally long polyglutamine tracts in the mutant proteins. The result is a selective loss of neurons with a different anatomical distribution for each disorder. The genetic defects have been established but the mechanism(s) by which the mutant proteins initiate the specific pathogenic processes remains to be elucidated. HD is the most common and best studied CAG disease resulting from a CAG expansion in the huntingtin gene, which causes the protein to misfold and form amyloid-like inclusions in the brain. Downstream consequences include abnormal protein-protein interactions, transcriptional disregulation, and mitochondrial dysfunction, however, the precise etiology of this disease is unknown. The quality of the speakers, including younger as well as more established researchers, constitutes a major focus of attraction. Their diverse backgrounds and broad range of expertise (molecular and clinical) were critical aspects that guided our choices. This Symposium is intended to promote the understanding of molecular mechanisms operating in the polyglutamine diseases, especially in HD, a topic that has been less explored in previous FENS meetings.

The speakers will be:

Chiara Zuccato, University of Milano
“The neuronal function of huntingtin, the protein involved in Huntington’s disease”

Marian DiFiglia, MGH – Harvard Medical School
“The Role of Huntingtin Proteolysis in the Pathogenesis of Huntington's Disease”

Paul Muchowski, University of Washington
“A genomic screen in yeast implicates kynurenine 3-monooxygenase as a therapeutic target for Huntington’s disease”

Erich Wanker, Max Delbruck Centrum fur Molekulare Medizin
“Development of therapeutic strategies for amyloid diseases

MIND - MGH

I would like to tell you a bit about the MassGeneral Institute for Neurodegenerative Disease (MIND).
The Institute was established to accelerate research discoveries that will lead to treatment and cures – sooner, rather than later. A team of world-renowned experts together with young, innovative researchers are now working in a center that allows them to collaborate, strategize, and share technology to move from basic research to treatment for these diseases. As promising leads are developed in one area, they can be tested in the other neurodegenerative disorders.
Since many of the researchers at the Institute are physician-scientists, translating basic research to clinical applications that will improve the lives of patients is at the core of the MIND’s mission. The MassGeneral Institute for Neurodegenerative Disease’s model of collaboration and sharing of resources will hasten the pace of discovery and, we hope, change the prognosis for these diseases in this generation.
Learn more at http://adams.mgh.harvard.edu/cagn/

World PD Congress

The World Parkinson Congress will take place in Washington DC, in February 2006. This will be a great opportunity for scientists to discuss the latest and greatest advances on PD research. You can learn more about it at http://www.worldpdcongress.org/