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Impact of late-onset Alzheimers risk factor on synapse biology and endocytic trafficking
Portugal ( PorMSIC) - Nova University of Lisbon, Lisbon
Neuronal Trafficking in Aging Lab, CEDOC, NOVA Medical School
Claudia G. Almeida
Claudia G. Almeida
Type of Research Project
- Basic science
What is the background of the project?
Plaques are a defining neuropathological hallmark of Alzheimers disease and the major constituent of plaques, the B-amyloid peptide, is considered to play an important role in the pathophysiology of Alzheimers disease. B-amyloid plaques were thought to form from the gradual accumulation and aggregation of secreted B-amyloid in the extracellular space. More recently, the accumulation of B-amyloid has been demonstrated to occur within neurons with Alzheimers disease pathogenesis. Moreover, intraneuronal B-amyloid accumulation has been reported to be critical in the synaptic dysfunction, cognitive dysfunction and the formation of plaques in Alzheimers disease. However, it is unknown what causes B-amyloid accumulation in late-onset Alzheimers disease and the mechanism whereby B-amyloid is involved in pathogenesis have been unknown. Several candidate genetic risk factors were identified and we are now characterizing their impact on B-amyloid accumulation and on synapse function.
What is the aim of the project?
Overexpression of mutant genes or silencing their expression will be done in primary cortical neurons. Beta-amyloid levels will be quantified and synapse number and content determined, in order to study the influence of the expression of those genes.
What techniques and methods are used?
We will use Immunofluorescence, microscopy analysis and western blot techniques in order to quantify the β-amyloid levels and study the content and synapse number in each sample.
What is the role of the student?
- The student will observe the practical experiments but will be highly involved in the analysis of the results
- The tasks will be done under supervision
What are the tasks expected to be accomplished by the student?
The student should understand the scientific question and the methodology used. All work will be done, firstly, with supervision in order to give the student enough time to understand the procedures and learn from observation. But after learning the techniques, hopefully the student will easily perform some experiments on his/her own. If so, the student will be able to perform various different techniques, such as immunofluorescence, microscopy analysis and western blot techniques.
Will there be any theoretical teaching provided (preliminary readings, lectures, courses, seminars etc)
Acquirement of technical competences to perform cell culture techniques, cell biology and neuroscience techniques. Moreover, the student will acquire knowledge in biochemistry, molecular biology and genomics.
What is expected from the student at the end of the research exchange? What will be the general outcome of the student?
- The student will prepare a presentation
What skills are required of the student? Is there any special knowledge or a certain level of studies needed?
Laboratory experience is a most but not required.
Are there any legal limitations in the student’s involvement
Type of students accepted
This project accepts: - Medical students - Graduated students (less than 6 months)
- Ubelmann et al ; 2017.
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