ITR: Gene Design for Vaccines and Therapeutic Phages

疫苗和治疗性噬菌体的基因设计PI：Steven Skiena疫苗和抗生素已被证明分别是对抗病毒和细菌感染的非常重要的药物。 然而，目前的疫苗对某些病毒（如鼻病毒）无效，对其他病毒（如天花）有潜在危险。 此外，细菌耐药性菌株的进化已经成为治疗疾病（如结核病）的关键问题，我们建议利用遗传密码中固有的冗余来创造更安全、更有效的疫苗和一类改进的抗菌剂。我们应用设计和合成技术来替换病毒基因，使它们编码与野生型病毒相同的蛋白质，但方式不同。 对于第一个应用，我们试图通过引入改变翻译效率和RNA二级结构而不影响蛋白质编码的突变来削弱病毒株，从而产生更好的候选疫苗。对于第二个应用，我们试图通过消除重要的限制性位点来增强噬菌体（攻击细菌的病毒），以提高其对抗病原体感染的能力。PI（Skiena）是一位计算机科学家，他在理论序列设计问题上做了大量工作，这些问题是寻找编码特定蛋白质的优化DNA序列，同时实现其他目标。共同主要研究者（维默）是一位微生物学家，他在2002年7月通过完全从现成成分合成脊髓灰质炎病毒而引起了全世界的关注。但是，一旦你可以从头开始合成一个现有的基因组，你也可以做同样的新的和更好的设计。我们将合作开展一系列使用脊髓灰质炎病毒的计算和湿实验室实验，以测试和发展这一愿景。拟议研究的更广泛影响包括通过开发新型医疗疗法对社会的好处，以及其对跨学科生物信息学教育的影响。

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.