C. elegans essential genes

我的实验室研究的是一种名为秀丽线虫(线虫)的模型生物。它是被科学家选为“模型”的一小群精英有机体中的一员，也就是说，它是其他动物的替代品。它们(酵母、果蝇、线虫、斑马鱼和老鼠)都是世界各地数百个(如果不是数千个)实验室密集研究的对象。它们每一个都具有使它们在研究各种复杂程度的生物现象方面特别有价值的特性。秀丽线虫是这一精英群体的最新成员。它的世代时间短(3.5天)，后代众多(约300)，是透明的，拥有完全测序的基因组，并拥有最好的生物数据库之一，用于整理遗传、分子和基因组数据。线虫也是一种复杂的有机体，具有多种细胞类型，具有多节段的肠道、皮肤(皮下)、结构化的神经系统、排泄系统和复杂的性腺。我的研究重点是高等生物体中遗传信息的结构，特别是产生对有机体生存至关重要的产物的基因的性质和位置。秀丽线虫的全基因组测序(于1998年完成)是解决这类问题时使用的一个很好的有机体。生物体的遗传计划包含大约20,000个可识别的基因。我的实验室专注于在实验室条件下生存和有效繁殖所需的子集。线虫中有2500多个必需基因(与果蝇和老鼠的数量相似)。我的实验室已经在500多个这些基本基因中发现了突变变异(导致可检测到的变化的突变)。这些都是生物学各个方面的非常丰富的信息来源。我们的基本基因突变导致了在控制细胞增殖、细胞-细胞信号传递的性质、能量代谢和基因调控等方面的发现。在这笔赠款中，我建议使用最先进的分子基因组方法继续我们的基本基因发现工作，包括对整个遗传信息内容进行DNA测序。

My laboratory works with a model organism called Caenorhabditis elegans (the nematode). It is in a small elite group of organisms that have been chosen by scientists as "models", that is to say surrogates for other animals. They (yeast, the fruit fly, the nematode, zebrafish, and the mouse) are all intensively worked on by hundreds, if not thousands of laboratories around the world. They each have properties that make them particularly valuable for investigating biological phenomena at various levels of complexity. C. elegans is the most recent entry into this elite group. It has a short generation time (3.5 days), numerous progeny (about 300), is transparent, has an entirely sequenced genome, and has one of the best organismal databases for collating genetic, molecular, and genomic data. C. elegans is also a complex organism with many cell types, having a multi-sectional gut, skin (hypoderm), structured nervous system, excretory system, and complex gonad. My research has focused on the structure of genetic information in higher organisms and specifically the nature and location of genes that produce products that are essential for survival of the organism. C. elegans, with its fully sequenced genome (completed in 1998), is an excellent organism to use when working on this type of problem. The genetic plan of the organism contains about 20,000 recognizable genes. My laboratory has focused on the subset that are required for survival and efficient reproduction, under laboratory conditions. There are more than 2,500 essential genes in C. elegans (similar number to the fruit fly and mouse). My lab has identified mutational variants (mutations that cause detectable changes) in over 500 of these essential genes. These have been a very rich source of information for a variety of aspects of biology. Our essential gene mutations have lead to discoveries in the control of cell proliferation, the nature of cell-cell signaling, energy metabolism, and gene regulation, to name a few. In this grant, I propose to continue our work on essential gene discovery using state of the art molecular genomic approaches, including DNA sequencing of the entire genetic information content.