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Creation of non-antibody, synthetic, peptide-binding proteins

Primary Supervisor: Professor Anna V. Hine, Life & Health Sciences

Secondary Supervisor: Dr Andrew J Sutherland

PhD project title: Creation of non-antibody, synthetic, peptide-binding proteins

University of Registration: Aston University

Project outline:

The successful student will join the existing PRe-ART team and will be based at Aston University. Predictive Reagent Antibody Replacement Technology (PRe-ART) is led by Prof. Andreas Plückthun (University of Zurich), with collaborating PIs Prof Anna Hine (Aston University) and Prof Birte Höecker (University of Bayreuth, Germany). PRe-ART will create a foundational new technology platform to replace conventional reagent antibody technology. In a multidisciplinary approach combining basic science, protein engineering and computational prediction, PRe-ART is generating non-antibody components which can be combined in an entirely modular fashion to create molecules that bind any peptide of choice. Such a biotechnological revolution is timely because of current failings in the reagent antibody market.

The fundamental objective of the project is to change the way how binding proteins are generated.

For forty years, biological research has relied on monoclonal antibodies (mAbs) to detect biomolecules within medical diagnostics and basic life science research (reagent antibodies are not used in therapy, rather, they are used in vitro to detect biomolecules in virtually all biological and biomedical research, and also in clinical diagnostics). Without them, detection of disease-state biomarkers would be impossible and indeed, much fundamental life science research is absolutely dependent on mAbs. Yet unfortunately, it has become more and more evident that many mAbs are not nearly as specific as presumed, many mAbs are very poorly characterized and their production is based on unstable cell lines. In fact, about half of the commercial reagent mAbs have been shown to not function correctly.

The present project will solve this problem by the creation of protein modules, specific for very short stretches of peptide chains, from which modular binders (whole proteins) can be assembled.

The project will combine advances from protein design, evolutionary protein engineering, design of highly specified DNA libraries, advances from structural biology to enable the creation of such novel proteins.

BBSRC Strategic Research Priority: Renewable Resources and Clean Growth: Industrial Biotechnology: Understanding the rules of life: Structural Biology

Techniques that will be undertaken during the project:

  • Non-degenerate gene library synthesis
  • Next generation sequencing and bioinformatic analysis
  • Production of synthetic proteins
  • Assay development
  • Via collaboration: exposure to X-ray crystallography, display technologies and advanced molecular modelling.

Contact: Professor Anna Hine, Aston University