In recent years it has become increasingly clear that dysfunctional glia (astrocytes and microglia) play a major role in the pathogenesis of Alzheimer’s disease. In specific, lipid droplets haven been shown to accumulate in the Alzheimer’s disease brain, where they inhibit proper immune activation of astrocytes and microglia. In our lab we have established an iPSC-multiomics pipeline that has provided valuable new insights into the molecular pathways underlying lipid- and immune dysfunction downstream of genetic risk factors for Alzheimer’s disease such as ApoE4. In this PhD project, you will apply this previous knowledge to develop cellular screening assays in order to identify novel candidate interventions for Alzheimer’s disease.
You will work with an experienced team to translate our previous findings on glial lipid biology and inflammation to assays for drug discovery and CRISPR screening. Your goal is to set up a scalable cellular assay for relevant immunometabolic phenotypes in ApoE4 glia. Once established, you will execute a drug, or CRISPR, screen to identify novel candidate interventions and targets. You will validate your findings in an array of cellular iPSC-models present in the lab, compare these to known iPSC- and human patient datasets and define a mechanism of action. You will then work with an (inter)national team of collaborators to select the best candidate interventions and move these forward into translation studies in mice or humans.
The research will be conducted at the Amsterdam Alzheimer Center, an (inter)national leading center in the field of top clinical care and high-quality scientific research into dementia. The Alzheimer Center Amsterdam is a stimulating workplace with more than 100 employees where an informal atmosphere goes hand in hand with ambitions and attention to personal development.
During the publication period, applications will be handled continuously. If the vacancy is filled, it will be closed prematurely.
If you have any questions about this position, please feel free to contact Rik van der Kant, via r.h.n.vander.kant@vu.nl.
For more information about the application procedure, please contact Chey Edwards, Recruitment Advisor, via c.i.edwards@amsterdamumc.nl or via +316 214 87 245.
A reference check, screening and hiring test may be part of the procedure. Read here whether that applies to you. If you join us, we ask you for a VOG (Certificate of Good Conduct).
Internal candidates will be given priority over external candidates in case of equal suitability.
Acquisition in response to this vacancy is not appreciated.