PhD position

Abnormalities in sensorimotor integration in mTORopathies – underlying mechanisms and potential treatments | 1,0 fte

About this position

The candidate will study the mechanisms underlying sensorimotor integration problems in mTORopathies, aiming to identify possible treatments, as described in more detail below:

Problem: The mechanistic target of rapamycin (mTOR) pathway is a highly complex and conserved signaling cascade involved in biomass synthesis, growth and cell proliferation. Specifically, during brain development, it has been proposed that a tight regulation of mTOR signaling is required for sustaining cell cycle length and re-entry, defining pluripotency status and triggering differentiation. Therefore, mutations along this pathway frequently lead to complex monogenic neurodevelopmental disorders (also known as mTORopathies), characterized by vast and heterogeneous phenotypes that can include increased prevalence of immunodeficiencies and malignancies, as well as megalencephaly, epilepsy, intellectual disability and autism spectrum disorder. However, there are currently only a handful of treatments available that address these neurological symptoms, all with significant adverse effects.

Solution: There are currently no biomarkers that can predict the level of intellectual disability or the severity of the ASD deficits in patients with mTORopathies. Interestingly, new insights suggest that sensorimotor network deficits, which reflect underlying brain dysfunction, have a high predictive value for determining neurodevelopmental phenotypes. People with ASD, for example, often present with sensorimotor deficits, which could be easily measured and potentially used as a marker for early diagnosis. Thus, the validation and establishment of new sensorimotor tools that enable a quicker and objective identification of neuropsychiatric phenotypes is critical.

Plan: In this project, the PhD student will investigate, through in vivo approaches and cell cultures, the cascade of events in mouse models of human mTOR-pathway disorders that lead from specific mutations to sensorimotor deficits. The resulting understanding of the mechanisms underlying sensorimotor deficits will be used to then the ability of potential treatments to alleviate the deficits.

Approaches: This work will utilize electrophysiological recordings, microscopy and imaging techniques, combined with various behavioral tasks to analyses sensorimotor (in)abilities. The student will then test different intervention methods, including ultrasound-triggerable drug delivery systems developed by the consortium. The treatment methods will be tested first in organotypical slices and human iPSC cerebellar cultures before applying them to mouse models.

Profile

We are looking for a highly motivated and goal-oriented researcher with a M.Sc. degree in nanobiology, neuroscience, cell biology, biophysics, biomedical sciences, or related field. The ideal candidate has a background in molecular techniques (qPCR, Western blots etc.), behavioral techniques and electrophysiology, and is interested in learning how to use neuronal cell cultures to answer neurobiological questions in health and disease. The candidate should be fluent in English, have basic knowledge of at least one coding language (Pyton or MATLAB) and be motivated to work in an ambitious and collaborative research team.

About this Flagship

Within Convergence Health & Technology we work on groundbreaking research and innovation, bundled in 10 internationally leading research flagships. These are aimed at major breakthroughs in the fields of health and science.

This project is part of the Convergence program Integrative Neuromedicine, a large-scale collaborative effort from Erasmus University, Erasmus Medical Center and Delft University of Technology to develop integrated biological and computational models of the human brain. The PhD student will be part of the Badura and Schonewille labs, but interact regularly with the other project members for different aspects of the project.

To achieve this goal, our flagship team includes fundamental scientists, engineers, philosophers, psychologists, and clinicians across the three different institutions to converge towards a personalized integrative medicine approach. We want to combine data from all scales, from birth to deathbed, to understand the evolution of neurological disorders. We will start with identifying common biomarkers involved in these disorders. Our research will enable early diagnosis and improve potential treatments over time. Furthermore, we will show how new technology can be developed and used to achieve medically effective personalized treatment, while providing a comfortable and satisfactory experience from the individual’s perspective.

Our flagship project’s effectiveness, cohesiveness, and sustainability lie in the complementary ingenuity of interdisciplinary team members, our extensive network of academic and industrial partners, and the multiple sponsors seeking groundbreaking research. Ultimately, we will establish a pipeline that eases the transition from the bench to bedside through various breakthroughs to improve the subjects’ quality of care and quality of life.

Flagship Integrative Neuromedicine

What we offer

Following Erasmus MC policy:

  • You will receive a temporary position for 4 years at Erasmus MC
  • The gross monthly salary is € 2.631 ,- in the 1st year and increases to € 3.336,- in the 4th year (scale OIO).
  • There are excellent fringe benefits, such as a 13th month that is already paid out in November and a personal travel budget.
  • You will receive pension insurance with ABP. The employer covers approximately 2/3 of the monthly contribution.
  • Also included: special benefits, such as a physiotherapist and a company bicycle repairer. And there is also a sports club where you can work on your fitness after work.
  • An International Office which aids you in preparing for your journey and stay

The terms of employment are according to the Collective Bargaining Agreement for Dutch University Medical Centers (CAO UMC).

About Convergence

Today’s urgent and complex societal challenges call for convergence; crossing boundaries between institutions and disciplines to create new perspectives and solutions. This is why TU Delft, Erasmus MC and Erasmus University Rotterdam are joining forces in what is referred to as: the Convergence. Within the Convergence theme of Health & Technology, we form new frameworks that promote scientific discoveries and technological innovation in the field of health and healthcare.

Erasmus MC stands for a healthy population and excellence in healthcare. By conducting groundbreaking work, we aim to push boundaries through leading the way in research, education and healthcare. We have access to the latest equipment and techniques in a state-of-the-art environment.

The Department of Neuroscience at Erasmus MC, Rotterdam is a dynamic and collaborative environment of about 150 people across 22 research groups. The PhD candidates will work in a motivated small team with close supervision by Dr. Aleksandra Badura and Dr. Martijn Schonewille. 

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Additional information

For more information about this vacancy, please contact Dr. Aleksandra Badura, Principal Investigator, e-mail: a.badura@erasmusmc.nl

Apply for this position

Are you interested in this vacancy? Please apply before 31 December 2022

Please upload the following information in English (pdf format only):

1.         Letter of motivation (generic letters will be disregarded),

2.         Detailed CV with publication list

3.         High school transcripts (grades)

3.         Three names of potential references

Your application for this position can be sent to healthandtechnology@convergence.nl