Seminar: A quantitative synthetic-biological approach to optimization of therapeutic fusion proteins
Event Details
- Date:
- Thursday, 18 July 2019
- Time:
- 11:00 am - 12:00 pm
- Room:
- Seminar Room, Level 1, AIBN (Building 75)
- UQ Location:
- Australian Institute for Bioengineering and Nanotechnology (St Lucia)
- Event category(s):
Event Contact
- Name:
- Jessica Kirkbride
- Phone:
- 64215
- Email:
- j.kirkbride@uq.edu.au
- Org. Unit:
- Australian Institute for Bioengineering and Nanotechnology
Event Description
- Full Description:
- Abstract
Natural protein-protein interactions can be harnessed to engineer protein therapeutics with improved target specificity and delivery. The molecular geometry of the relevant proteins is crucial for fine-tuning drug design. Using these principles, in one line of experiments we constructed a tissue-targeted form of erythropoietin that stimulates red blood cell production without triggering platelet production or thrombosis. Erythropoietin was directed to red blood cell (RBC) precursors and mature RBCs by fusion to an anti-RBC antibody V region. Many such constructs activated EPO receptors in a glycophorin-dependent manner in vitro and stimulated RBC but not platelet production in mice. Some fusion proteins enhanced thrombosis in mice and caused adhesion between RBCs and EPO receptor in trans. Based on a protein-structural model of the RBC surface, we rationally designed an anti-RBC/EPO fusion that does not induce adhesion in vitro or enhance thrombosis in vivo. Our results indicate how meso-scale geometric considerations can inform design of synthetic-biological systems.
Bio
Jeff’s current research interests are in therapeutic protein development and synthetic biology. As a senior staff scientist at the Wyss Institute and Harvard Medical School, he has developed new approaches to genetic circuit design and targeting drug activity to specific tissues to avoid side effects. Previously he was Director of Structural Biology and Director of Intellectual Property at EMD Serono, a major protein-focused pharmaceutical company, where he designed protein drugs. He has published numerous articles on drug development, synthetic biology, nervous system development, and bacterial genetics, and holds several patent applications and issued patents. He received his Ph.D. and B.A from Harvard University.
Directions to UQ
- Google Map:
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- Directions:
- St Lucia Campus | Gatton campus.
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