ITR: Gene Design for Vaccines and Therapeutic Phages

点击翻译按钮获取中文摘要

Gene Design for Vaccines and Therapeutic PhagesPI: Steven SkienaVaccines and antibiotics have proven to be tremendously important agents against viral and bacterial infections, respectively. However, current vaccines are ineffective against certain viruses (e.g. rhinovirus) and potentially dangerous against others (e.g. smallpox). Further, the evolution of antibiotic-resistant strains of bacteria has become a critical problem in treating diseases such as tuberculosis.We propose to exploit the redundancy inherent in the genetic code to create both safer and more effective vaccines and an improved class of anti-bacteriological agents. We apply design and synthesis techniques to replace viral genes so they code for identical proteins as in the wild type virus, but in different ways. For the first application, we seek to weaken viral strains by introducing mutations that alter translational efficiency and RNA secondary structure without affecting protein coding so as to create better vaccine candidates. For the second application, we seek to strengthen bacteriophages (viruses which attack bacteria) by eliminating important restriction sites so as to improve their ability to combat pathogenic infections.The PI (Skiena) is a computer scientist who has worked extensively on theoretical sequence design problems which seek optimized DNA sequences which code for a particular protein while simultaneously accomplishing some other objective. The co-PI (Wimmer) is a microbiologist who attracted worldwide attention in July 2002 by synthesizing poliovirus completely from off-to-shelf components. But once you can synthesize an existing genome from scratch, you can do the same for new and better designs as well. We will collaborate on a series of computational and wet lab experiments using poliovirus to test and develop this vision.Broader impacts of the proposed research include benefits to society through developing new types of medical therapeutics, and its impact on interdisciplinary bioinformatics education.