PhD student neurodegeneration and protein quality control

The Princess Máxima Center for Pediatric Oncology is the largest childhood oncology center in Europe, in which basic, preclinical, and translational research is collectively dedicated at advancing the understanding of pediatric cancer and treatment thereof. The institute aims to provide the highest level of care for all children with cancer and has the ambition to cure all children of cancer and improve quality of life. The research department offers state-of-the-art core facilities (including organoid and imaging facilities) and an interdisciplinary and collaborative environment.

Within the subgroup of Willianne Vonk, part of the Hoeijmakers group, we are seeking a highly enthusiastic and ambitious PhD candidate that is interested in being part of a larger national program aimed at better prediction of disease onset and progression of and developing therapeutic interventions for polyglutamine (polyQ) diseases, in particular spinocerebellar ataxia- 1 and -3 and Huntington’s disease (Nederlandse Wetenschaps Agenda, project CureQ.  Are you our candidate? We would like to meet you!

The Research Group

The research group studies the consequences of aging-related, DNA damage-induced genome instability and transcription stress for neuronal health, and the therapeutic potential of nutritional interventions in this, aiming at improving the quality of life of children cured from cancer.

Neurobehavioral morbidity in childhood cancer survivors affects important aspects of cognitive function (including attention, memory, processing speed, intellect, executive functions, academic achievement, and emotional health). These deficits may have major life-long impact on the quality of life, ability to develop, and career and socio-economic prospects of ex-cancer patients, and strongly resemble late-onset neurodegenerative pathologies of the brain (e.g., Alzheimer’s and Huntington’s disease).

Impairment of protein quality control during brain aging may provoke protein misfolding and accumulation into amyloid inclusions, contributing to the onset and progression of these neurodegenerative diseases. Within the Vonk subgroup, we are interested to gain detailed understanding on the fundamental mechanisms mediating the preservation of neuroplasticity and its attenuation with age and in disease, with a focus on protein quality control and the chaperonin TRiC/CCT. TRiC/CCT functions at different levels to preserve neuronal health (e.g., maintenance of proteome solubility and robustness of cellular stress responses), yet, it’s expression is for currently unknown reasons attenuated during brain aging and in Huntington’s disease.

The position

This position is one of three PhD projects within the national CureQ consortium that collectively will work on the goal of defining ‘novel modulators of disease onset and progression’. The PhD position at the Princess Máxima Center in Utrecht will focus on gaining functional understanding and exploring modes to stabilize or boost the expression of (spatial) protein quality control determinants to slow down or revert protein aggregation and associated neurodegeneration in polyQ diseases, with a particular focus on the TRiC/CCT chaperonin complex. Besides cellular models for polyQ diseases, the study will involve (patient-derived) iPSC and organoid models.

Profile

We are looking for a highly motivated team player with excellent English communication skills, who is passionate about fundamental biological questions on the principles of protein aggregation and neurodegeneration. You have a Master’s degree in Neuroscience, Life Sciences, Biomedical Sciences or an equivalent field. ‘Hands-on’ experience and in-depth knowledge of cell biology (e.g. cell culture, confocal microscopy, flow cytometry) and molecular biology (e.g. cloning, gel electrophoresis) are strongly preferred. You will be working closely together with other group as well as CureQ consortium members, and you are enthusiastic to present your data and share your knowledge in a multidisciplinary setting.

  • Enthusiastic, highly motivated, result-driven, and self-initiative capacity
  • Creative, problem solver and analytical thinker with excellent social and organizational abilities
  • Proficiency in written and spoken English
  • You can work independently as well as in a collaborative setting 

Working at the Princess Máxima Center for Pediatric Oncology  

We offer a PhD project in an inspiring and interdisciplinary research environment. You will initially be appointed on a full time PhD position for a period of 1 year (36h/week), and your performance will be evaluated by a training and supervision plan. Upon satisfactory completion of the first year, your contract will be extended with three more years to a four-year PhD trajectory. The position is fully funded by the Dutch Science Organization (NWO, the NWA program).

Salary according to FWG 45 increment 6 (for the first year, increased to FWG 45 increment 10 in case of renewal), with 8,33% holiday allowance and 8,33% end-of-year bonus. The Princess Máxima Center operates according to the collective labor agreement ‘cao algemene ziekenhuizen’.

Apply for this position?

You can apply for this position by pressing the apply button on this screen. We would like to receive a letter of motivation, detailed CV, BSc and MSc grade list, and name and contact details of 2 references. Deadline for the application is February 22, 2023, but review of promising applications can start earlier. Selected canadidates will be contacted for (on-site) interviews.

You are welcome to contact Dr. Willianne Vonk for additional information about the vacancy.

Acquisitie naar aanleiding van deze vacature wordt niet op prijs gesteld.

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