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.
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
- Evaluate the kinetics of the enzymatic cleavage of chromogenic substrates containing an arginine residue attached to a chromophore to determine enzyme-substrate specificity
- 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.
We are looking for a PhD student with the following skills:
- 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
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.
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.
29 August 2018
INT – 0488
FOR ANY ENQUIRIES ABOUT THIS INTERNSHIP03 8344 1785