Determining the Specificity of Commercially Available Thrombin Substrates

Location: Parkville, VIC

Duration: 5 months

Proposed start date: TBC

Keywords: Biomedical science, enzyme kinetics, thrombin generation

Please note: Due to funding requirements, students must have Australian Citizenship or Permanent Residency to apply. Any applicants not meeting this requirement will be ineligible for this project.

Project Background

Thrombin generation (TG) is a laboratory method that is increasingly being used in multiple clinical settings for evaluation of bleeding and clotting outcomes. Whilst TG provides a global assessment of haemostasis, the main problem associated with this laboratory method is the lack of standardisation. Specifically, TG uses multiple substrates that are based on different methods of thrombin detection (e.g. chromogenic, fluorogenic) and inter-operator differences associated with manual set-up. However, a factor that has been discussed but not investigated is whether the substrates used to detect thrombin are specific to thrombin and/or whether they interact with other plasma proteins.

Research to be Conducted

  1. Evaluate the kinetics of the enzymatic cleavage of chromogenic substrates containing an arginine residue attached to a chromophore to determine enzyme-substrate specificity
  2. Evaluate the kinetics of the enzymatic cleavage of chromogenic substrates containing an arginine residue attached to a fluorophore to determine enzyme-substrate specificity

The specificity of the substrates will be measured using a plate-reader, a number of which are available within the company for the intern to use.

Skills Required

We are looking for a PhD student with the following skills:

Essential

  • A fundamental understanding of enzyme kinetics and experience measuring these parameters
  • Must possess basic laboratory skills including the ability to pipette accurately, handle proteins appropriately, and operate scientific instrumentation
  • Must be able to apply good scientific methods, and be capable of keeping detailed laboratory notes

Expected Outcomes

This will be the first study to investigate the specificity of frequently used thrombin substrates. Understanding the specificity of thrombin substrates is critical for accurate interpretation of thrombin generation results, a factor that is critical in providing the best possible care for hospitalised patients. At the completion of this project we hope to have characterized, in detail, the specificity of commonly used chromogenic and fluorogenic thrombin substrates.

Additional Details

The intern will receive $3,000 per month of the internship, usually in the form of stipend payments.

It is expected that the intern will primarily undertake this research project during regular business hours, spending at least 80% of their time on-site with the industry partner.  The intern will be expected to maintain contact with their academic mentor throughout the internship either through face-to-face or phone meetings as appropriate.

The intern and their academic mentor will have the opportunity to negotiate the project’s scope, milestones and timeline during the project planning stage.

Applications Close

 29 August 2018

Reference

INT – 0488

FOR ANY ENQUIRIES ABOUT THIS INTERNSHIP

03 8344 1785
contact@aprintern.org.au