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NPC Top Publications

June 2012

Genes & proteins involved in the regeneration of the small intestine uncovered

The Netherlands Proteomics Centre (Heck group) in collaboration with the Hubrecht Institute (Clevers group, Alexander van Oudenaarden group, presently still at the Department of Physics, MIT, Cambridge, USA) made a significant advance in understanding the molecular basis that program the regeneration of tissue through the stem cells in the intestine. Joint efforts from these groups allowed the identification of genes and proteins that are specifically expressed in the stem cells of the intestine and that allow this tissue to regenerate. These results have been jointly published in The EMBO Journal on June 12, 2012.

Stem cells receive special attention in the scientific community and in society. This has been inspired by their potential to differentiate into tissues and there use in regenerative medicine. A lot of progress has been made towards the application of stem cells in therapy. Hans Clevers explains: “with our current knowledge it is possible to isolate these stem cells from the intestine and generate organoids in the lab that quite resemble the tissue”. To achieve successfully cellular replacement therapies it is still far from the bedside: “All future applications of stem cells will depend on exquisite understanding of the mechanisms that regulate stem cell biology” ads Clevers. Traditionally, research on stem cells has been focused on the study of a small group of genes, one of them, Lgr5, led Clevers and co-workers to the identification of the stem cells in the intestine and other tissues. However, during the last decade emerging technologies, such as proteomics, have allowed scientists to study thousands of players in the reprogramming process simultaneously. “Our research focused on the identification, in a global fashion, of genes and proteins that are uniquely expressed in the intestinal stem cells and how they behave when stem cells differentiate” says Albert Heck.  In this report, 510 genes were identified to be uniquely expressed in these cells, including Lgr5, defining a stem cell signature. “This is an important first step, providing a clear picture of the molecular signature that provides these cells with their unique properties” explains Javier Munoz, first author on the paper.

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May 2012

Protease bias in absolute protein quantitation

Trypsin is the most commonly used protease in typical proteomics experiments. (Absolute) Quantitation using spectral counts provides insight into protein abundances. NPC researchersnow show in Nature Methods this is  dependent on the protease used. In other words, the use of a single protease, such as trypsin, can introduce biasses in the observed protein abundances. 

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March 2012

Spatially resolving the secretome of the fungus Aspergillus niger

The fungus Aspergillus niger is a commercially-important producer of organic acids and industrially-relevant enzymes. Pauline Krijgsheld from the Kluyver Centre for Genomics of Industrial Fermentation, and colleagues from the Netherlands Proteomics Centre, determined quantitatively the so called secretome of different, concentric zones of a fungal colony. These zones reflect the age of the fungal mycelium. Krijgsheld found that a major part of the secreted proteins are retained in the fungal cell wall.

Treatment with the drug cycloheximide released these proteins in the culture medium due to partial degradation of the cell wall. This finding may impact yield and composition of protein mixtures obtained during growth of Aspergillus niger in industrial bioreactors. The results were published in the Journal of Proteome Research.

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