Postdoc positions ALS grant

For a grant by the Dutch ALS foundation

We will use 2D, 3D in vitro and in vivo models to examine how signals from specific senescent cells may contribute to the disease and whether this can be targeted.

Dit ga je doen

Amyotrophic lateral sclerosis (ALS) is a life-threatening neurodegenerative disease for which there are currently no effective treatments. Current research efforts often address protein deregulation as a contributing factor. Our proposal is to examine the environment of motor neurons in greater detail to determine how this contributes to the disease, with a specific focus on a subtype of cellular senescence.

Senescence is a state that cells can enter when they become irreparably damaged. Senescent cells secrete factors into their environment that can lead to chronic disruption of cell-to-cell communication. Recent evidence in mice has shown that senescent cells can drive cognitive decline, neuroinflammation and neurodegeneration. Our preliminary research has also identified the presence of senescent cells in TDP43 mutant mice. Understanding and counteracting the potentially deleterious role of senescent cells in the environment may therefore be attractive against ALS.

You will investigate whether the removal of scarred-senescent cells can affect motor neuron health and function in 2D and 3D tissue culture, assess the role of potential candidates using advanced multiplex techniques (4i, Cy-Chi and CosMX), and evaluate whether disease features can be stalled or counteracted in neurodegeneration/aging/ALS mouse models. When successful and the elimination of scarred senescent cells delays or counteracts disease features in mice, this innovative strategy could then progress into clinical translation aimed at improving the quality of life and survival of patients.

Hier ga je werken

Utrecht University and its Medical Center house well over 6000 researchers and consistently delivers top-notch research in biology and medicine, evident from a solid ranking among the absolute top academic centers in Europe.

The Center for Molecular Medicine houses experts and state-of-the-art facilities for a broad range of techniques, including genomics (next-generation DNA sequencing, metabolomics, proteomics), cell culturing (iPS cells, organoids), microscopy (live cell imaging, electron microscopy) and bioinformatics (high-performance computing).

Peter de Keizer is associate professor in "Senescence in Cancer and Aging". His aim is to unravel the molecular mechanisms that cause cells to become senescent and to identify how these cells drive aging and age-related diseases. The research has a strong translational component and a spearpoint of the group is to develop methods to target the deleterious effects of senescent and senescent-like cancer cells, for instance by eliminating them altogether.

Dit neem je mee

This 3-year postdoctoral fellowship is focused on molecular mechanisms in ALS (Amyotrophic Lateral Sclerosis), especially involving mouse models and iPSC-derived co-culture systems. Applicants interested in this project should meet the following requirements:

• You have recently completed your PhD in a biological or biomedical discipline, or will do so soon.
• 5+ years background in molecular and cellular biology. A background in neuroscience or neurodegeneration is a strong preference.
• An understanding of neurology-related biology and genetics (e.g., with ALS markers such as SOD1, C9orf72, TDP-43, FUS), where hands-on experience with associated model systems is much preferred.
• Willingness to work with animal models, including support with mouse colony management and (basic) genotyping, behavioral assays (e.g., rotarod, grip strength, gait analysis). Experience in this area is a plus.
• Experience with 2D cell culture, preferably iPSC systems, and a willingness to invest considerable time and effort into optimization of 3D coculture systems and Air-Liquid Interface cultures.
• Experience with -omics is preferred.
• Experience with tissue collection and processing of tissues, including histology and immunohistochemistry is preferred.
• A track record of scientific publications or publications in late-stage review.
• Willingness to participate in scientific writing (manuscripts, reports, grants) for additional project funding.
• Ability to work independently and collaboratively, and willing to supervise other lab members where needed (Technicians, PhD/MSc students).
• Willingness to co-organize and actively participate in physical and online meetings and conferences.
• Ensuring compliance with legal requirements as reviewed by a competent in-house and/or external legal counsel for laboratory work and scientific communication.
• Use best efforts to secure at least one top-tier publication at the end of the project.
• Maintaining confidentiality on all internal organizational affairs.