Therapeutic strategies for Huntington''s disease

Job summary

A postdoctoral position is available in Professor Jordi Alberch laboratory. The position involves working with a team of scientists studying therapeutic strategies for neurodegenerative disorders, particularly for motor disorders affecting the basal ganglia.

The programme is a continuation of works recently published in Canals et al., 2004, J.Neurosci., 24:7727-39; del Toro et al., 2006, J. Neurosci., 26:12748-57; del Toro et al., 2009, Mol Biol Cell., 20:1478-92; Giralt et al., 2010, Gene Ther., Epub ahead of print; Gines et al., 2010, J Biol Chem., Epub ahead of print, which have underscore that BDNF is involved in Huntington’s disease (HD) and it is a good candidate to be used as a neuroprotective tool for the treatment of HD.

The present project will be performed in the laboratory of Pathophysiology of Neurodegenerative disorders in the Department of Cell Biology, Immunology and Neurosciences at the , Medical School, University of Barcelona. This multidisciplinary group is leaded by Dr Jordi Alberch, Professor, with more than 20 years of experience in the study of the regulation of trophic factors expression and their neuroprotective effects in different experimental models of neurodegenerative diseases of the basal ganglia. In the last years, we have focused our studies on the relevance of BDNF in the pathophysiology of HD. To show a direct involvement of BDNF in the pathophysiology of HD, we developed a new transgenic mouse model of HD with lower levels of BDNF. We crossed the R6/1 mouse model of HD with BDNF+/- mice, showing that reduced BDNF levels induced an early onset and more severe pathology. We have also demonstrated that the pathological features of HD can be reverted by exogenous BDNF delivery by direct intracerebral injections and by ex vivo cell-mediated strategies. We have also recently developed a new approach by obtaining engineered astrocytes that express high levels of BDNF under the GFAP promoter.

The group is integrated in the Spanish network of neurodegenerative disorders (CIBERNED) and in the Spanish Cell Therapy network (RETICS; TERCEL). These two networks provide a collaborative environment to successfully achieve our objectives.

The purpose of this programme of work will be:

• Looking for new strategies for BDNF delivery ex vivo for clinical purposes by genetic manipulation of stem cells.
• Search and test small molecules that activate the BDNF receptor in vitro and in vivo.

2. The project is likely to involve some or all of the following techniques:

• Biocomputering
• Drug design
• Molecular techniques, cloning, lentiviral constructs, transfection, arrays...
• Human stem cell cultures.
• In vitro studies.
• Biochemistry: western blots, ELISA,
• In vivo administration of cells and drugs
• Behavioral analyses, motor and cognitive
• Histology

Main Duties

To conduct research investigating the potential application of different strategies of BDNF and related molecules as therapy approaches for neurodegenerative disorders.

Duties and Responsabilities

• To contribute to the design and planning of experiments in relation to this project
• To develop a thorough understanding of the research field and be involved in the intellectual decision making process required for successful completion of the project
• To set up and run experiments in consultation with the Principal Investigator
• To record, analyse and write up the results of experiments and ensure that laboratory notebooks are kept fully up to date as a formal record of the research
• To prepare and present findings of research to the Principal Investigator and other members of the centre
• To prepare progress reports on research
• The post holder may be required to perform some limited teaching and/or supervision of other members of staff and/or students, under the guidance of the Principal Investigator
• Responsible for ensuring that designated equipment is safe and maintained in good working order
• As duties and responsibilities change, the job description will be reviewed and amended in consultation with the post holder
• The post holder will carry out any other duties that are within the scope, spirit and purpose of the job, as requested by the Principal Investigator

Person specification

Knowledge and Qualifications

Essential:

• Undergraduate degree in a life science discipline
• PhD in an appropiate life science discipline

Desirable:

• Basic knowledge of Neurosciences
• Publications in high impact factor peer reviewed journals

Skills

Essential:

• Abilitity to develop ideas logically and design experiments to test hypotheses
• Ability to modify and apply new methods to advance a project
• Ability to analyse and write up data for presentations and publications
• Ability to present complex information effectively to a range of audiences
• Effective written and verbal communication skills
• Ability to meet deadlines
• Record of delivering high quality research

Desirable:

• Research skills in Molecular techniques (cloning, lentiviral constructs, transfection), Biochemistry (Western blot, ELISA), immunohistochemistry and immunocytochemistry.
• Expertise in in vivo approaches
• Ability to direct junior members of the laboratory in simple laboratory procedures

Experience

Essential:

Experience of working in a research environment

Desirable:

Experience of multi-disciplinary working

Personal Qualities

Essential:

• Commitment to high quality research
• Ability to work effectively as part of the team
• Ability to work independently and to use own initiative when required

(Read eligibility criteria)