Prosiectau fesul blwyddyn
Crynodeb
While schistosomiasis remains a significant health problem in low to middle income countries, it also represents a recently recognised threat to more economically-developed regions. Until a vaccine is developed, this neglected infectious disease is primarily controlled by praziquantel, a drug with a currently unknown mechanism of action. By further elucidating how Schistosoma molecular components cooperate to regulate parasite developmental processes, next generation targets will be identified. Here, we continue our studies on schistosome epigenetic participants and characterise the function of a DNA methylation reader, the Schistosoma mansoni methyl-CpG-binding domain protein (SmMBD2/3). Firstly, we demonstrate that
SmMBD2/3 contains amino acid features essential for 5-methyl cytosine (5mC) binding and illustrate that adult schistosome nuclear extracts (females > males) contain this activity. We
subsequently show that SmMBD2/3 translocates into nuclear compartments of transfected murine NIH-3T3 fibroblasts and recombinant SmMBD2/3 exhibits 5mC binding activity. Secondly,
using a yeast-two hybrid (Y2H) screen, we show that SmMBD2/3 interacts with the chromo shadow domain (CSD) of an epigenetic adaptor, S. mansoni chromobox protein (SmCBX). Moreover, fluorescent in situ hybridisation (FISH) mediated co-localisation of
Smmbd2/3 and Smcbx to mesenchymal cells as well as somatic- and reproductive- stem cells confirms the Y2H results and demonstrates that these interacting partners are ubiquitously
expressed and found within both differentiated as well as proliferating cells. Finally, using RNA interference, we reveal that depletion of Smmbd2/3 or Smcbx in adult females leads to significant reductions (46±58%) in the number of proliferating somatic stem cells (PSCs or neoblasts) as well as in the quantity of in vitro laid eggs. Collectively, these results further expand upon the schistosome components involved in epigenetic processes and suggest that pharmacological inhibition of SmMBD2/3 and/or SmCBX biology could prove useful in the development of future schistosomiasis control strategies.
Iaith wreiddiol | Saesneg |
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Rhif yr erthygl | e1007107 |
Cyfnodolyn | PLOS Pathogens |
Cyfrol | 14 |
Rhif cyhoeddi | 6 |
Dynodwyr Gwrthrych Digidol (DOIs) | |
Statws | Cyhoeddwyd - 28 Meh 2018 |
Ôl bys
Gweld gwybodaeth am bynciau ymchwil 'Methyl-CpG-binding (SmMBD2/3) and chromobox (SmCBX) proteins are required for neoblast proliferation and oviposition in the parasitic blood fluke Schistosoma mansoni'. Gyda’i gilydd, maen nhw’n ffurfio ôl bys unigryw.Proffiliau
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Karl Hoffmann
- Cyfadran Gwyddorau Daear a Bywyd, Gwyddorau Bywyd - Professor
Unigolyn: Dysgu ac Ymchwil
Prosiectau
- 2 Wedi Gorffen
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BBSRC Core Strategic Programme in Resilient Crops: Grasslands Gogerddan
Armstead, I., Donnison, I., Jones, H., Skot, L., Fernandez Fuentes, N., Phillips, D., Kingston-Smith, A. & Bosch, M.
Biotechnology and Biological Sciences Research Council
01 Ebr 2017 → 31 Maw 2020
Prosiect: Ymchwil a ariannwyd yn allanol
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Flatworm DNA methylation: deciphering the mark and characterising the machinery
Biotechnology and Biological Sciences Research Council
15 Ebr 2013 → 14 Ebr 2016
Prosiect: Ymchwil a ariannwyd yn allanol
Y Wasg / Y Cyfryngau
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Parasitic flatworms affect millions in developing countries, but new research offers hope
28 Meh 2018 → 29 Meh 2018
2 Cyfraniadau cyfryngau
Y Wasg / Cyfryngau: Cyfraniad y Cyfryngau