This collaborative project is embedded in the Amsterdam Institute for Infection and Immunity and is funded by the ADORE Foundation.
ADORE, which stands for
Amster
Dam
Oncology and Neuroscience
REsearch, is a collaborative effort between the Cancer Center Amsterdam and Amsterdam Neuroscience, comprising a total of over 2,000 researchers. It represents a bold and innovative approach to medical scientific research. Under this concept, our foremost cancer researchers and neuroscientists will collaborate to unravel the most pressing issues related to cancer and brain diseases, such as dementia and MS.
Immune responses in the central nervous system (CNS) have opposing effects on disease outcome. The altered brain microenvironment and consequent attraction of (auto)reactive immune cells into the CNS are key detrimental events in neurological disorders, such as dementia and multiple sclerosis (MS), and contribute to disease pathology. In contrast, in brain tumors, the CNS micro-environment actively limits the infiltration of tumor reactive immune cells, while stimulating accumulation of immune suppressive immune cells. These opposite effects may drive on local alterations in the CNS microenvironment that alter during disease onset and progression.
However, to date we lack fundamental understanding of underlying pathways that control immune cell infiltration (T cells and myeloid cells) in these opposite (suppressive/ permissive) situations in the brain. The overall aim of this ADORE Crossing Barriers consortium is therefore to define how the brain microenvironment controls immune cell infiltration into the CNS during health and in MS and dementia vs. glioblastoma (GBM) and brain metastatic lung tumours and melanoma.
In this specific post-doc project, we will conduct fundamental research
- Into which mechanisms underlie immune cell migration across the brain barriers in context of mentioned diseases.
- To decipher the role of the altered brain microenvironment in this process.
As a postdoc, you will develop immune competent brain organoids based on iPSC technology that mimic disease setting and connect them to the brain barriers using various human
in vitro platforms. Identified pathways critical for the altered CNS immune responses will be modulated in appropriate humanized models using either CRISPR/CAS9 or lentiviral technology or via pharmacological manipulation and the subsequent effect on immune cell activation and trafficking will be determined.