Inhertied and acquired platelet function defects

Summary

Bleeding defects in Australian patients and families will be characterised using genomic and proteomic analysis

Supervisor(s)

Professor Chris Ward

Research Location

Northern Blood Research Centre, Northern Clinical School

Program Type

Masters/PHD

Synopsis

Platelets are anucleate particles which repair blood vessel damage and prevent blood loss. Defects in platelet function lead to abnormal bleeding patterns, which can be life-threatening. We have characterized a number of patients with recessive defects of critical adhesion molecules, and used haplotype analysis to show a common origin among European families in the case of one particular mutation. Ongoing studies are examining a large Australian family with a unknown combined defect affecting platelet function and red cell morphology. Functional studies and protein biochemistry have identified target molecules for genetic analysis. The student will learn a wide range of functional assays used to characterize platelet function, including aggregometry, flow cytometry and cone-and-plate adhesion. S/he will gain expertise in biochemical methods including 2-D gel electrophoresis and prepare samples for proteomic analysis. Isolation, amplification and sequencing of platelet DNA and RNA, including real-time PCR will be used to identify the responsible mutation(s) in this and other families. These findings will provide the basis for a rapid screening test to identify affected individuals. The student may also have the opportunity to test the effects of target mutations in vivo, using mammalian cell expression systems.

Additional Information

Techniques for this project include:

• Platelet function mapping, using optical and impedance aggregometry, flow cytometry and automated analysers
• Proteomic analysis of platelet lysates and signaling pathways
• Genomic screening for aberrant expression profiles and identification of target genes

Keywords

abnormal bleeding, Platelet function testing, Adhesion receptors, Platelet signaling pathways, Genetic disorders, Heart & circulation, Human body

Opportunity ID

The opportunity ID for this research opportunity is: 190