Project details

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Stem cells and oncogenesis in a novel model organism

Keywords:
cancer stem cells DNA damage response

Researchers:
Prof. dr. E.V. Berezikov
dr. D. Olivieri

Nature of the research:
Fundamental research aimed at developing a new system in a clinical direction

Fields of study:
cell biology oncology molecular biology

Background / introduction
The stem cell theory of cancer postulates that stem cells are at the origin of most cancer types due to their proliferative potential. As more and more evidence accumulates in support of this hypothesis, model organisms that allow the study of stem cell behavior in vivo are being increasingly sought after.
Macrostomum lignano is a marine flatworm with extensive regenerative potential and a rising model organism due to its abundant population of totipotent stem cells, which confers to Macrostomum a unique advantage compared to more traditional models.
This and other features make Macrostomum an ideal model to study carcinogenesis and stem cell transformation in vivo.
Research question / problem definition
The aim of this project is to develop Macrostomum lignano as model for cancer research.
The two main objectives are:
1) developing an inducible hyperproliferation model in Macrostomum;
2) identifying and characterizing proto-oncogenes and tumor suppressor genes in Macrostomum lignano.
Workplan
The most recent and advanced molecular biology techniques are already established in Macrostomum lignano, making genetic manipulation and gene knock down possible.
This project will require the development of transgenic animals, antibody validation, immunoprecipitation and mass spectrometry, gene knock-downs, phenotypic analysis and immunohistochemistry.
During the project the student will also learn all the techniques to independently work with Macrostomum lignano.
References
1. http://www.macgenome.org
2. Regeneration: The origin of cancer or a possible cure? NJ Oviedo,WS Beane, 2009.
3. Planarian PTEN homologs regulate stem cells and regeneration through TOR signaling. NJ Oviedo, et al., 2008.
4. The Retinoblastoma pathway regulates stem cell proliferation in freshwater planarians. SJ Zhu, BJ Pearson, 2012.
5. Planarians as a model system for in vivo tumorigenesis studies. DJ Schaeffer, 1993.
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