PhD Student in Neuroimmunology
We recently found evidence in post mortem brain analyses that brain tissue-resident memory T (Trm) cells drive ongoing inflammatory demyelination in advanced MS. We have reported the presence of small numbers of brain Trm cells in human normal white matter and identified the perivascular space as the compartment where the majority of brain Trm cells reside under normal conditions. In brains from donors with advanced MS, we encountered extensive clustering of large numbers of Trm cells in perivascular cuffs and infiltration of Trm cells into normal-appearing white matter and MS lesions. Inflammatory active lesions were most enriched with recently activated Trm cells. These data indicate that CNS compartmentalized reactivation and mobilization of brain Trm cells in the perivascular space is a critical event in MS-lesion formation in progressive MS.
We hypothesize that Trm cells and/or resident perivascular macrophages in late MS to display a changed configuration of receptors and ligands relevant to Trm-cell clustering, reactivation, and mobilization. To test this hypothesis, we will study Trm cells in advanced MS with focus on their spatial contacts, transcriptional profile, migratory characteristics, and effector functions. We will address these aspects using post-mortem brain tissue and viable brain T cells obtained with a very short post-mortem delay from MS brains of the NBB using immunohistochemistry, flow cytometry, RNA sequencing and a number of in vitro assays. We anticipate that our research can lead to new disease-modifying treatments for progressive MS, targeting checkpoints for brain Trm-cell activation in the perivascular space.
We are looking for an excellent and highly motivated candidate, trained in neurobiology and immunology, with a keen interest in neurological diseases. Experience with gene expression profiling, bioinformatics, flow cytometry, cell culture, and immune histochemistry is important.
This position involves a temporary appointment of 4 years. The first appointment is for one year with the option for an extension for the remaining period pending on an evaluation.
The gross monthly salary coming with a fulltime appointment will amount to a minimum of € 2395,- in the first year to €3061,- in the fourth year (P-scale of the Collective Agreement for Dutch Universities; CAO-NU), excluding 8% holiday allowance and 8.3% year-end bonus. We offer an extensive package of fringe benefits, such as travel expenses, paid parental leave, flexible working hours, 30 days paid leave per year and assistance in finding an accommodation.
Netherlands Institute for Neuroscience (NIN) located next to the Amsterdam UMC, location AMC.
Information and Application
Dr. J. Smolders (e-mail: [email protected], tel: 06-26026987) and Dr. J. Hamann (e-mail: [email protected], tel: 06-31519376). Please, send a letter of application including your curriculum vitae and two references to the above addresses before January 15, 2021.