Investigation of the Interplay between Blood Cells and the Endothelium in Microfluidic Devices

Location: Parkville, VIC

Duration: 5 months

Proposed start date: ASAP

Project Background

CSL Limited is a global specialty biotechnology company that researches, develops and manufactures products to treat and prevent serious human medical conditions. CSL’s product areas include blood plasma derivatives, vaccines, anti-venom and cell culture reagents used in various medical and genetic research and manufacturing applications. More recently, CSL has developed recombinant versions of coagulation factors VIIa, VIII and IX and von Willebrand factor (VWF). Research is ongoing to further optimise these recombinant proteins and develop additional proteins related to haemostasis and thrombosis.

Further to CSL’s research in haemostasis and thrombosis, microfluidic technologies are being developed to study these processes in a reproducible manner that recapitulates microvascular physiology and pathophysiology in vivo. Since cellular interactions are important in the vasculature, and endothelial cells play a key role in these interactions, endothelialisation of microfluidic devices will be established and tested.

A fundamental understanding of vascular physiology and the ability to culture endothelial cells are essential skills for this project. The intern should possess basic laboratory skills including the ability to perform aseptic techniques, pipette accurately, handle proteins appropriately, and operate scientific instrumentation, including a microscope. The applicant must be able to apply good scientific methods and be capable of keeping detailed laboratory notes.

Research to be Conducted

The primary objective of this project is to establish a vascularised microfluidic system to mimic the flow conditions prevalent in small arteries and arterioles in vivo. This will be done by coating the inner surface of microchannels with a layer of human umbilical vein endothelial cells. The commercial microfluidic devices (Bioflux plates) are fabricated from microscopy-compatible materials so that haemostatic and thrombotic processes can be imaged in real-time.

Human whole blood from healthy volunteers will be flowed at different shear rates through the endothelialised channels in the presence or absence of pharmaceutical reagents to determine the effect of these reagents on haemostatic parameters.

The resources required include a Bioflux microfluidic system that is designed to run automated shear flow protocols and has the capability to be coated with cellular monolayers. This system is currently available at CSL. Requisite microscopy and cell culture facilities are also available.

Skills Required

ESSENTIAL

  • Currently doing a PhD in microbiology, physiology, or closely related field
  • Basic laboratory skills including microscopy, aseptic cell culture techniques, pipetting
  • Ability to maintain detailed laboratory notes

Expected Outcomes

It is expected that the intern will determine the conditions necessary for culturing endothelial cells in microchannels. This will be important for enhancing the capabilities of the vascular biophysics laboratory at CSL. The expected outcome is a report summarising the methods and results obtained during the establishment of an endothelialised microfluidic system. It is predicted that these data will result in a publication. The preparation of this paper is outside the scope of the project, however due recognition will be given to the intern’s contribution to this body of work.

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

 27 February 2019

Reference

APR – 0827