Gene regulatory and protein-protein interaction networks in stress and disease

Main area:Protein chemistry
Target group:Biochemistry, Molecular Biomedicine, Biology
Educational level:Bachelor, Masters
Project description:

Living cells depend on regulated gene expression, which in turn depends on recognition of specific promoter sequences by gene specific transcription factors. Gene regulatory networks describe how transcription factors associate with downstream target genes. These networks can be expanded to describe the complex links with upstream regulators and between numerous proteins. The understanding of how living organisms function depends on unraveling of these biological network, and the overall objective of the research in our group is to increase the understanding of specific networks. In particular, we investigate how cells react to stress exposure at the molecular level, and how molecular structure is important to these reactions. Currently, we investigate the following:

  • How do stress-associated transcription factors target specific genes and what are the target genes of importance to stress responses? Collaboration with Fred de Masi, Technical University of Denmark, and Klaas Vandepoele, Gent University.
  • How do stress-associated members of the NAC transcription factor family interact with other proteins, and how do these interactions lead to agonistic and antagonistic cooperation?
  • How does protein intrinsic disorder contribute to regulatory interactions of stress-associated transcription factors, and how can knowledge about protein intrinsic disorder obtained in vitro be translated to the in vivo organismal level? Collaboration with Martin Willemoës and Birthe Kragelund, BIO.
Methods used:Quantitative real-time PCR, applied bioinformatics, chromatin immunoprecipitation (ChIP), protein design, protein binding microarray, protein production and purification, biochemical assays, fluorescence and circular dicroism spectroscopy, isothermal titration calorimetry, genetic selection, transgenic complementation
Keywords:Gene regulatory network, Transcription factor, Protein-protein interactions, Intrinsic disorder, Thermodynamics
Supervisor(s): Karen Skriver
Email:kskriver@bio.ku.dk