Dataset Information

Natural genetic variation on proteome level in Caenorhabditis elegans

ABSTRACT: Natural genetic variation is the raw material of evolution and influences disease development and progression. To analyze the effect of the genetic background on protein expression in the nematode C. elegans (Caenorhabditis elegans), the two genetically highly divergent wild-type strains N2 (Bristol) and CB4856 (Hawaii) were compared quantitatively. In total, we quantified 3,238 unique proteins in three independent SILAC (stable isotope labeling by amino acids in cell culture) experiments. The differentially expressed proteins were enriched for genes that function in insulin-signaling and stress response pathways.

INSTRUMENT(S): LTQ Orbitrap

ORGANISM(S): Caenorhabditis Elegans

TISSUE(S): Whole Body

SUBMITTER: Polina Kamkina

LAB HEAD: Michael Otmar Hengartner

PROVIDER: PXD002010 | Pride | 2016-03-11

REPOSITORIES: Pride

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Dataset's files

Source:

			Action	DRS
	20120514_02_N2lCBh_7to19.CID.ITMS.iso.apl	Other
	20120514_02_N2lCBh_7to19.CID.ITMS.peak.apl	Other
	20120514_02_N2lCBh_7to19.CID.ITMS.secpep.sil0.apl	Other
	20120514_02_N2lCBh_7to19.CID.ITMS.secpep.sil1.apl	Other
	20120514_02_N2lCBh_7to19.CID.ITMS.sil0.apl	Other

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Publications

Natural Genetic Variation Differentially Affects the Proteome and Transcriptome in Caenorhabditis elegans.

Kamkina Polina P Snoek L Basten LB Grossmann Jonas J Volkers Rita J M RJ Sterken Mark G MG Daube Michael M Roschitzki Bernd B Fortes Claudia C Schlapbach Ralph R Roth Alexander A von Mering Christian C Hengartner Michael O MO Schrimpf Sabine P SP Kammenga Jan E JE

Molecular & cellular proteomics : MCP 20160304 5

Natural genetic variation is the raw material of evolution and influences disease development and progression. An important question is how this genetic variation translates into variation in protein abundance. To analyze the effects of the genetic background on gene and protein expression in the nematode Caenorhabditis elegans, we quantitatively compared the two genetically highly divergent wild-type strains N2 and CB4856. Gene expression was analyzed by microarray assays, and proteins were qua ...[more]

PMID: 26944343

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Project description:Infections and diseases caused by parasitic nematodes have a major adverse impact on the health and productivity of animals and humans worldwide. The control of these parasites often relies heavily on the treatment with commercially available chemical compounds (anthelmintics). However, the excessive or uncontrolled use of these compounds in livestock animals has led to major challenges linked to drug resistance in nematodes. Therefore, there is a need to develop new anthelmintics with novel mechanism(s) of action. Recently, we identified a small molecule, KM08948, with nematocidal activity against the free-living model organism Caenorhabditis elegans. Here, we evaluated KM08948’s potential as an anthelmintic in a structure-activity relationship (SAR) study in C. elegans and in the highly pathogenic, blood-feeding Haemonchus contortus (barber’s pole worm), and explored the compound-target relationship using thermal proteome profiling (TPP). First, we synthesised and tested a series of 25 KM08948 analogues for nematocidal activity in both H. contortus (larvae and adults) and C. elegans (young adults), establishing a preliminary nematocidal pharmacophore for both species. We identified several compounds with marked activity against either H. contortus or C. elegans which had greater efficacy than KM08948, and found a significant divergence in compound bioactivity between these two nematode species. We also identified a KM08948 analogue, 25, that moderately inhibited the motility of adult female H. contortus in vitro. Subsequently, we inferred three H. contortus proteins (HCON_00134350, HCON_00021470 and HCON_00099760) and five C. elegans proteins (F30A10.9, F15B9.8, B0361.6, DNC-4 and UNC-11) that interacted directly with KM08948; however, no conserved protein target was shared between the two nematode species. Future work aims to extend the SAR investigation in these and other parasitic nematode species, and validate individual proteins identified here as targets of KM08948. Overall, the present study describes an evaluation of this anthelmintic candidate and highlights some challenges associated with early anthelmintic discovery.