Belgium: PhD Project ‘Identifying molecular keystones in neurodegenerative brain disease networks’ at University of Antwerp

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Project description

Neurodegenerative brain diseases, such as like Alzheimer’s disease (AD), frontal temporal lobar degeneration (FTLD) and Parkinson’s disease (PD) are age-related disorders that due to our increasingly elderly population are becoming more prevalent each year. In the absence of a cure or preventive strategy, the number of dementia patients worldwide is projected to reach over 100 million in 2050.

The VIB-Department of Molecular Genetics has generated considerable insight into the genomic basis of these disorders. The next logical step forward in this research is to try and understand how these genomic alterations then actually generate the disease pathophysiological phenotype. Recent research has demonstrated that the phenotypic generation of the disease requires a molecular ‘translation’ through a network of facilitating genes/proteins, i.e. the disease ‘signature’. This translating network therefore represents two important topics for neurobiological research, i) discovery of the crucial network nodes of genes/proteins that propagate and maintain the pathophysiology and, ii) generation of ‘network’ therapeutic targets whose modulation may exert an amplified and reinforced therapeutic action. The components (genes/proteins) of the molecular disease signature therefore should comprise a minimal, but comprehensive, condensation of the disease process at a level that both facilitates a thorough appreciation of the disease but also provides a tractable framework for therapeutic development.

Therapeutic intervention at the level of the molecular signature will likely engage multiple endogenous signaling systems that will likely synergize to reinforce the potential therapeutic effects of the remedial agent. Until now, pharmacotherapeutics have been devised often with just single molecular targets in mind and have unfortunately often proven ineffective for a wide range of patients, especially for complex disorders such as AD. Hence, rather than considering disease as the perturbation of a single gene/protein factor, the appreciation of disease as the deformation of a complex network of factors in the disease signature would suggest that the most efficacious treatments would restore the balance of as many components of the deformed signature to achieve its therapeutic effects. Our primary goal therefore is to determine which factors control these networks, the molecular ‘keystones’, and then target these with experimental therapeutics.

We will apply an integrated approach of multiple post-genomic modes of investigation, i.e. transcriptomics, quantitative proteomics, metabolomics and bioinformatics to biomaterials (e.g. plasma, cerebrospinal fluid, lymphoblast cell lines, brain tissue) from disease-identified patients. Using the information gathered from these streams we will then generate therapeutic strategies to re-align the pathophysiological disease signatures, primarily through regulation of the network ‘keystone’ factors.

The VIB Department of Molecular Genetics has a long-standing expertise in the molecular genetics of Dementia and related disorders, and has contributed significantly to the current knowledge of the genetic etiology of AD, FTLD and PD. The department has a centralized genetic service facility that allows high throughput processing of the samples and data. DNA extraction, establishment of lymphoblast cell lines and computational analyses are also centralized.

 

Context

The VIB Department of Molecular Genetics is one of 8 research departments of VIB (http://www.vib.be/VIB/EN/). With near 100 researchers working in 5 research groups, the department aims to understand the complex nature of neurological human diseases (http://www.molgen.ua.ac.be/). The department disposes over the expertise of centralized service facilities like the Genetic Service Facility and the Diagnostic Service Facility, as well as central units with expert knowledge in functional genomics, technology development and bio-informatics.

The VIB Department of Molecular Genetics is located at the University of Antwerp (http://www.ua.ac.be/), and is affiliated with the Institute Born-Bunge, a research institute with a track record in clinical neurological and pathological research into CNS and PNS diseases (http://www.bornbunge.be/Home/index_nl.shtml), and to the faculty department of Biomedical Sciences of the Faculty of Pharmaceutical, Biomedical and Veterinarian Sciences.

Candidate profile

  • Motivated students of all nationalities with a strong commitment to basic and/or clinical research.
  • Holder of a MSc in medical or biomedical sciences, biochemistry, biotechnology or biology.
  • Fluent in English (spoken and written language).
  • Any experience in genetics, genomics or molecular cell biology is an advantage.
  • The candidate should have well-developed social skills directed to working in a team.

Application:

If you are interested in this position, mail a letter of interest, curriculum vitae (including a list of publications) and the names of 2-3 reference persons to phdmolgen.vib-ua.be mentioning ‘TN group’.

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