Powered by OpenAIRE graph
Found an issue? Give us feedback

University of Konstanz

University of Konstanz

Funder
Top 100 values are shown in the filters
Results number
arrow_drop_down
134 Projects, page 1 of 27
  • Funder: European Commission Project Code: 753054
    Overall Budget: 171,461 EURFunder Contribution: 171,461 EUR

    Mutations in the giant muscle protein titin are a major cause of heart disorders in human populations. Routine DNA screening of patient cohorts is now becoming feasible, with a staggering number of titin truncations and missense single nucleotide polymorphisms (mSNPs) rapidly accumulating in genomics databases (>17,000 mSNPs). While the link between titin truncation and disease is now becoming clarified, detecting the pathogenic potential of mSNPs remains a substantial challenge. In mSNPs classification, bioinformatics evaluation is a necessary first filtering step, but existing predictors are poorly reliable. To address this problem, we aim to develop a new titin-centric scoring function that predicts the mechanistic effect of an mSNP exchange in the titin protein by considering the specific characteristics of its poly-domain chain. For this work, we will build a medium-throughput molecular diagnostic pipeline that harvest existent structural models of titin components in estimating mSNPs-induced changes in free energy and conformational dynamics in the protein. Calculations will be benchmarked against experimentally obtained biophysical and biochemical data. To develop this methodology, we will use a clinically pertinent training set of 75 mSNPs. However, in a subsequent step, stable predictions will be extrapolated to the rest of the titin chain by exploiting the repetition of structural and functional loci within the chain. A titin map of vulnerability “hot-spots” so calculated will be distributed to the research community. Ultimately, we aim to produce a tool that can aid clinicians to identify patients at risk of developing a titin-based heart condition at early disease stages, where intervention is still possible.

    visibility1K
    visibilityviews1,306
    downloaddownloads1,074
    Powered by Usage counts
    more_vert
  • Funder: European Commission Project Code: 273180
    more_vert
  • Funder: European Commission Project Code: 339834
    visibility2K
    visibilityviews2,270
    downloaddownloads2,667
    Powered by Usage counts
    more_vert
  • Funder: European Commission Project Code: 323977
    visibility9K
    visibilityviews9,064
    downloaddownloads9,529
    Powered by Usage counts
    more_vert
  • Funder: European Commission Project Code: 290876
    visibility12K
    visibilityviews11,671
    downloaddownloads11,419
    Powered by Usage counts
    more_vert

Do the share buttons not appear? Please make sure, any blocking addon is disabled, and then reload the page.

Content report
No reports available
Funder report
No option selected
arrow_drop_down

Do you wish to download a CSV file? Note that this process may take a while.

There was an error in csv downloading. Please try again later.