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As a source of new cells in the body, stem cells are responsible for maintaining healthy tissues. Functional decline of stem cell activity is one of the hallmarks and a major contributor to ageing. This is why we study ageing-resilient and highly regenerative animals – to understand the molecular and cellular mechanism that drive stem cell activity during regeneration and protect stem cells from intrinsic and extrinsic stresses.

Stem cell biology and ageing are intricately linked, and the investigation of the mechanisms that regulate the activity of stem cells and drive such processes as tissue regeneration and stem cell maintenance and protection are likely to contribute important knowledge to the science of ageing.

The ability to regenerate and protect stem cells from stresses varies broadly in the animal kingdom. While humans have only limited regeneration capacity and modest resistance to genotoxic stress, induced, for example, by ionising radiation, some animals, such as flatworms, can regenerate their whole bodies and sustain very high doses of radiation, and at the same time maintain an active stem cell compartment.

The questions that arise are:

  • What are the molecular mechanisms responsible for stem cells differentiation into various cell types?
  • How lost body parts regenerate to their original state and why do some animals regenerate, while others can not?
  • What are the molecular mechanisms responsible for the maintenance and protection of stem cells in stress- and ageing-resilient animals?
  • How the remarkable biological properties of highly regenerative and ageing resilient animals can be translated into anti-ageing and regenerative therapies?
Relevance

How our research benefits to society

Our laboratory develops and uses a model organism flatworm Macrostomum lignano. These animals have impressively advanced resilience, including ability to regenerate almost all body parts, go through long periods of starvation, and sustains very high doses of ionising and ultraviolet C radiation. There are three main interconnected research directions in the laboratory:

  • Regeneration is an efficient organismal resilience strategy but understanding its mechanisms is still incomplete at best. Using the power of transgenesis in M. lignano, combined with single cell sequencing, we characterise key transcription factors and chromatin states that drive cell fate specification during regeneration.

  • Damage to DNA is a major factor of ageing and cancer. Hence, preventing and efficiently repairing DNA damage must be one of the main organismal resilience strategies. We investigate how M. lignano survives high doses of gamma- and UVC radiation, focusing specifically on stem cells and combining transgenesis, genomics and proteomics approaches.

  • We demonstrated that M. lignano has an active ageing resilience genetic program based on maintenance of the stem cell compartment, and proposed that M. lignano can be a rich source of genetic information for molecular engineering of lifespan extension in other animals. We focus on testing this hypothesis and identifying pro-longevity genes by investigating candidates from M. lignano using a pyramid of species, including C. elegans, killifish and mouse.

    Alumni

    Frank Beltman (Technician, 2014-2017)
    Current position: Senior Analyst Flow Cytometry bij ICON (Assen, The Netherlands)

    Margriet Grelling (Technician, 2014-2017)
    Current position: Senior Technician GenomeScan (Leiden, The Netherlands)

    Philip Weissert (Postdoc, 2013-2018)
    Current position: Program Chair at Arqus European University Alliance (Styria, Austria)

    Ekaterina Ovchinnikova (Postdoc, 2013-2018)
    Current position: Senior Scientist at Mosa Meat (Maastricht, The Netherlands)

    Daniel Olivieri (Postdoc, 2013-2014)
    Current position: Senior Scientist at Roche (Basel, Switzerland)

    Jakub Wudarski (PhD student, 2012-2019).
    Current position: Specially Appointed Assistant Professor at National Institute for Basic Biology (Okazaki, Japan)

    Magda Grudniewska (PhD student, 2012-2017)
    Current position: Head of Biosafety Testing at GenomeScan (Leiden, The Netherlands)

    Katrien De Mulder (Postdoc, 2009-2011)
    Current position: Molecular Biologist at AZ Sint-Lucas Gent (Gent, Belgium)

    Turan Demircan (PhD student, 2009-2013)
    Current position: Associate Professor at Muğla Sıtkı Koçman Üniversitesi (Muğla, Turkey)

    Daniil Simonav (PhD student, 2008-2012)
    Current position: co-founder polvetra.ru

    Meltem Isik (PhD student, 2007-2012)
    Current position: Senior Scientist, Bioinformatics at Vor Biopharma (Cambridge, MA, USA)

Contact

University Medical Center Groningen (UMCG)
European Research Institute for the Biology of Ageing (ERIBA)
PO Box 196, Internal Zip Code FA50
9700 AD Groningen
The Netherlands

Visiting address
University Medical Center Groningen (UMCG)
European Research Institute for the Biology of Ageing (ERIBA)
Antonius Deusinglaan 1, building 3226
9713 AV Groningen