Computational Design of Novel Functional Proteins: Case Studies in Vaccine Design

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Event details

Date 27.03.2014
Hour 10:00
Speaker Bruno Correia, Ph.D., The Scripps Research Institute, La Jolla, CA (USA)
Location
Category Conferences - Seminars
BIOENGINEERING SEMINAR

Abstract:
The full capability to manipulate protein structure and function holds the promise to make transformative contributions in diverse scientific domains. Novel nanomaterials, enzymes and proteins with biomedical applications are all within the reach of protein engineers. Computational protein design has made critical contributions to enable structure-based design. Vaccine research could greatly benefit from new strategies to produce cheap and efficacious vaccines against pathogens that remain elusive to traditional approaches, becoming serious global health burdens. Rapid discovery and structural characterization of broadly neutralizing antibodies (bnabs) are quickly uncovering sites of vulnerability in pathogens. Computational methodologies have been developed to perform structure-based design of immunogens to re-elicit neutralizing antibodies against conserved epitopes, providing the foundation for epitope-focused vaccines. The designed immunogens mimic relevant epitope conformations recognized by bnabs and were dubbed epitope-scaffolds (ES). I will present two case studies for the design of epitope-scaffolds.

In a first case study, I will present the design of an HIV ES where we used computational design to guide in vitro evolution experiments and showed that this hybrid computational-experimental approach can accomplish challenging protein design problems.

In a second case study, I will present Rosetta Fold From Loops, a new method to fold and design novel proteins around functional sites of interest. I designed ESs to mimic an epitope from Respiratory Syncytial Virus, a relevant vaccine target. Remarkably, potent neutralization activity was elicited in ES immunized animals. These results provide a proof of principle for the use of ESs for vaccine development and support its potential to target other pathogens that remain elusive to vaccine development, like HIV and Influenza.

More generally, the results support that computational protein design can play an important role in generating novel proteins relevant for fundamental and biomedical research applications.

Bio:
2004 B.S. in Chemistry, Faculdade de Ciências e Tecnologia da Universidade de Coimbra (P)
2010 Ph.D. in Computational Biology, ITQB - Universidade Nova de Lisboa (P)

Current and Previous Scientific Activities:

2011-current  Research Associate, Department of Chemical Physiology, The Scripps Research Institute, La Jolla, CA (USA)
2006-2011  Ph.D. Student and Research Associate, University of Washington, Seattle, WA (USA)
2005-2006  Ph.D. Student, Instituto Gulbenkian Ciência (P)
2005  Research Technician, University of Warwick (UK)
2004  B.S. Student, University of Warwick (UK)
2003-2004  B.S. Student, Universidade de Coimbra (P)

Practical information

  • Informed public
  • Free
  • This event is internal

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