Computerized analysis and prediction of RNA structure and function

核糖核酸（rna）是细胞中最重要的分子之一。到目前为止，已经发现了600多个不同的RNA家族。其中之一，微rna，被发现与我们的基因如何产生有关。这一功能对我们的免疫系统、细胞如何分化和特化、癌症如何发生和发展以及细胞如何决定死亡都至关重要。人们相信，构建人工分子装置来控制这些细胞机制将有助于解决人类健康和治疗方面的许多问题，同时也有助于解决食品和能源生产以及环境方面的问题。然而，在我们能够设计出如此有效的设备之前，我们需要详细了解细胞如何在其基因生产功能中采用其行为。事实上，人们相信细胞的功能是通过一个非常复杂的基因调控网络来实现的，其中每个基因对其他几个基因都有影响。最近，基于rna的设备已经被设计成通过读取和靶向基因调控网络来处理和传输简单的细胞信息。在某些方面，这些设备可以被看作是作用于基因调控网络的小型计算机。为了建造这样的细胞计算机，我们需要知道它们的RNA成分的三维结构。然而，技术问题使我们无法使用经典的实验方法（例如x射线晶体学和核磁共振）来解决这些结构。梅杰博士是开发计算方法来确定RNA三维结构的专家，这是昂贵的实验方法的替代方法。他最近介绍了一种非常有前途的新方法，并于今年发表在著名的《自然》杂志上。在这项拨款申请中，他建议进一步发展这种新方法，特别是探索和分析基于rna的细胞计算机的动态组件。他的目标是把他的新算法交给实验学家，因为快速可靠地产生精确和准确的RNA 3D结构将为生物技术和生物医学领域带来巨大的好处。在本研究期间，Major博士将培养2 - 3名博士后和3 - 4名博士生。

Ribonucleic acids (RNAs) are among the most crucial molecules of the cell. So far, more than 600 different RNA families have been found. One of them, microRNAs, is found involved in how our genes are produced. This function is key to our immune system, to how our cells differentiate and specialize, to how cancer develops and progresses, and how our cells decide to die. It is believed that building artificial molecular devices to control these cellular mechanisms will help resolve many problems in human health and therapeutics, but also in food and energy production, and environment. However, before we can engineer such effective devices we need to understand in details how the cell adopt its behaviours in function of its gene production. In fact, it is believe that the cell functions using a very complex gene regulatory network, where each gene has an effect on several others. Recently, RNA-based devices have been engineered to process and transmit simple cellular information by reading and targeting the gene regulatory network. In some ways, these devices can be seen as small computers that act on the gene regulatory networks. In order to build such cellular computers, we need to know the three-dimensional structures of their RNA components. However, technical problems refrain us from resolving these structures using classical experimental methods (for example X-ray crystallography and nuclear magnetic resonance). Dr. Major is an expert in the development of computational methods to determine RNA three-dimensional structures, an alternative to costly experimental approaches. He recently introduced a new approach that is very promising, which was published this year in the renowned journal Nature. In this grant proposal, he proposes to develop further this new approach to especially explore and analyze the dynamic components of RNA-based cellular computers. He aims at putting his new algorithms in the hands of the experimentalists, since rapidly and reliably producing precise and accurate RNA 3D structures will yield immense benefits to the biotechnology and biomedical fields. During the term of this research, Dr. Major will train two to three postdoctoral trainees and three to four PhD students.