Difference between revisions of "Team:Ruperto Carola/Description"

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Revision as of 14:49, 3 July 2019

Project Inspiration and Description

Peptide-detection has been a major topic in the biotechnological community for several decades. The continuous developments in this field continue to improve early diagnosis in a wide range of diseases, setting new trends like personalized medicine or lab-on-a-chip methods which allow for detection of peptides in a wide size range, as well as ensuring high specificity and sensitivity.

These tools are largely available for peptides bigger than 15 kDa [1] , but there are still challenges present in the detection of smaller aminoacid chains. Because of this, improvements in small-peptide assays would allow the early detection of harmful pathogens, even before the immune response is initiated by the body. Our first thoughts turned towards neglected viral diseases like African swine fever (ASF) affecting pigs. Because of its long latency period, the virus is hardly detectable but easily transmitted in the early stages. Its impact on farmers is also growing - in recent years, ASF has grown into a major concern for the pork industry, with multiple outbreaks detected in eastern Europe, forcing several countries to tighten border controls and even stop pork import.

The prospect of simplifying the ASF detetction procedure, thus mitigating the risk for farmers, and wild boar populations, is what first inspired us to address the issue of developing a yeast based biosensor capable of detecting peptides of around 1.5 kDa. Extensive research on further possible applications made us realize the potential of such a system for revealing the presence of other biomarkers, such as for different metabolic disorders, cancers, environmental pollutants, as well as other topics such as detection of mirror biomolecules.

Using the yeast Ste2 mating receptor as a backbone, we will utilise a directed evolution approach to adapt the microorganisms to detect of a wide range of targets. Furthermore, we plan to set up a cell-to-cell communication pathway to explore the possibilities opened by the signaling of the many yeast cells in our living sensor, while we consider the possible adaptation of our project to in-vitro work. Cooperation and accesibility allows scientists to responsibly build upon existing knowledge, which is we will attempt to develop all the necessary bioinformatic tools for

  • Target selection —i.e. software which helps one choose the appropriate peptide target accessible to the receptor
  • Modelling of the receptor-ligand interactions in order to enable planning of optimal intermediate steps (substrate walking)
  • Adapting our wet-lab protocols and procedures to be useful for future yeast directed evolution projects.

[1]: Detection of a Peptide Biomarker by Engineered Yeast Receptors; Adeniran A. e, Sarah Stainbrook, John W. Bostick, and Keith E. J. Tyo; ACS Synthetic Biology 2018 7 (2), 696-705 DOI: 10.1021/acssynbio.7b00410