PhD Candidate in Neurobiology of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is characterized by profound and/or pathological fatigue and malaise. It can be aggravated by physical or cognitive efforts at intensities previously well tolerated by the individual. The symptoms are persistent or recurrent over long periods of time and lead to a significant reduction in functioning and cannot (yet) be explained by a somatic cause. Also the molecular and cellular mechanisms in the brain that underlie ME/CFS are currently not known.

We are looking for an ambitious and enthusiastic PhD candidate to help us unravel this largely unexplored, burdensome and complex disorder. The position is supported by a recently awarded ZonMw grant, and is part of a larger Dutch consortium on ME/CFS. This project concerns a collaboration between the University of Amsterdam (Brain Plasticity group, Swammerdam Institute for Life Sciences (SILS) in the Faculty of Science), the Amsterdam UMC and the Neuroimmunology group of the Netherlands Institute for Neuroscience (NIN). You will be working both at the SILS and at the NIN.

Research in our consortium aims at advancing fundamental knowledge of the neurobiology of ME/CFS, using state-of-the-art molecular methods in neuroscience. Together with societal partners, we aim to translate fundamental knowledge and novel insights into solutions for societal problems.

The aim of this project is to make first steps into improving our understanding the molecular and cellular alterations in the brain in relation to fatigue, such as they occur in ME/CFS and in Long Covid, for which we will use human post-mortem brain tissue and study related pre-clinical fatigue model systems (mice and/or primates).

Together with ME/CFS patient associations and the Netherlands Brain Bank, a brain donor program is initiated to make brain tissue of ME/CFS patients available for scientific research. Using the collected human brain tissue, you will characterize proxies for the stress response, microglia-neuron interactions, and energy/mitochondrial metabolism, all of which have been implicated in brain functioning and have been proposed to contribute to ME/CFS. The methods to be used are quantitative immunohistochemistry, STED microscopy, mitochondrial metabolic measures and (bulk, single cell and/or spatial) transcriptomics.

Are you fascinated by the human brain and the neurobiology of disease, and do you want to contribute to elucidating the brain mechanisms behind this debilitating disorder? Then this is the job for you!

What are you going to do?
You will help set up the donor program and assist in building the human ME/CVS brain cohort. You will perform a first, in-depth characterization of the brains of ME/CFS patients and their controls. You will study changes in (1) their HPA stress axis, (2) their resident immune cells, and (3) their mitochondrial energy metabolism, focusing on various brain regions; the hypothalamus, hippocampus, cortical grey matter and subcortical white matter of diagnosed ME/CFS, long-COVID and control brains using immunohistochemistry, flow cytometry, qPCR analysis and (single cell) RNA sequencing. A related project with TNO Rijswijk on fatigue after COVID involves the study of similar changes in relation to COVID infection in post-mortem primate brains.

Tasks and responsibilities:

• complete a PhD thesis within the official appointment duration of four years;
• work with pre-clinical disease models, such as mice and primates, as well as post mortem human tissue;
• use (single cell) RNA sequencing of post-mortem brain tissue to explore the changes in gene expression;
• use quantitative immunohistochemistry of corticotropin-releasing hormone (CRH) and

CRH/arginine vasopressin (AVP)-co-expression and glucocorticoid-receptor expression in hypothalamic

and hippocampal neurons to analyze HPA-axis activity;

• quantify and determine the phenotype(s) of microglia and T cells in cortical regions using quantitative

immunohistochemistry;

• explore mitochondria function and structure using qPCR and immunohistochemistry;
• perform experiments in a systematic and well-controlled manner and keep accurate records by properly

documenting and organizing your work;

• be an active member of the research groups and take responsibility for shared tasks. Discuss your work

with the group leaders, colleagues at all three institutes and during national consortium meetings.

Incorporate feedback and give input to others;

• take a leading role in writing manuscripts and incorporate subsequent feedback for improvement;
• participate in the ONWAR PhD training program;
• assist in teaching program at UvA and supervise Bachelor and Master theses and tutoring students.

You will get the opportunity to

• combine the advantages of a truly collaborative project, including access to the 3 different

state-of-the art research facilities at the UvA, TNO and NIN partners;

• publish your work in international journals, leading to a PhD thesis and present your

results at (inter)national scientific meetings;

• develop and expand you academic, professional, personal and soft skill set,

needed to become an independent scientist.

You are passionate about science and have a particular interest in neuroscience, neuro-immunology and disease mechanisms. You have experience with, or proven interest in quantitative immunocytochemistry and high-resolution microscopy, RNA-sequencing, qPCR and the use of computational analysis tools. You have a creative mind, excellent communication skills, the ability to work and troubleshoot independently and collaboratively and you look forward to work with cutting-edge of technology. Finally, you are a team player and can report well verbally and in writing, You are further a pleasant colleague who enjoys being part of an interdisciplinary team of neuroscientists and can handle and organize a multidisciplinary project and working in different environments.

Your experience and profile

• a recent MSc or MD degree, with relevant expertise, preferably in neuroscience,

neuro-immunology or medicine, or a related area of biomedical science;

• demonstrated hands-on experience with at least several of the following techniques:

qPCR, RNA sequencing, (high resolution) immunohistochemistry;

• fluent in English, both written and spoken.

A temporary contract for 38 hours per week for the duration of 4 years (the initial contract will be for a period of 18 months and after satisfactory evaluation it will be extended for a total duration of 4 years). The preferred starting date is 1 March 2024. This should lead to a dissertation (PhD thesis). We will draft an educational plan that includes attendance of courses and (international) meetings. We also expect you to assist in teaching undergraduates and master students.

Your salary will range between €2,770 in the first year to €3,539 gross per month in the last year of employment, on the basis of a full working week of 38 hours. This sum does not include the 8% holiday allowance and the 8.3% year-end allowance. A favorable tax agreement, the 30% ruling, may apply to non-Dutch applicants. The Collective Labour Agreement for Dutch Universities (CAO NU) is applicable.

Besides the salary and a vibrant and challenging environment at Science Park we offer you multiple fringe benefits:

• 232 holiday hours per year (based on fulltime);
• multiple courses to follow from our Teaching and Learning Centre; • a complete educational program for PhD students;
• the possibility to follow courses to learn Dutch;
• help with housing for a studio or small apartment when you’re moving from abroad.

Are you curious to read more about our extensive package of secondary employment benefits, take a look here.

The University of Amsterdam is the Netherlands' largest university, offering the widest range of academic programmes. At the UvA, 30,000 students, 6,000 staff members and 3,000 PhD candidates study and work in a diverse range of fields, connected by a culture of curiosity.

The Faculty of Science has a student body of around 8,000, as well as 1,800 members of staff working in education, research or support services. Researchers and students at the Faculty of Science are fascinated by every aspect of how the world works, be it elementary particles, the birth of the universe or the functioning of the brain.

The Swammerdam Institute for Life Sciences (SILS) is one of the Faculty of Science’s largest institutes. Its approximately 240 scientists and staff members work in 17 research groups that perform excellent research centered on four themes: Neurosciences, Cell & Systems Biology, Microbiology and Green Life Sciences.

Do you want to know more about our organization? Read more about working at the University of Amsterdam.