Neuronal RNA Biology

我们的DNA中的遗传信息被转录成信使RNA，然后翻译成蛋白质，后者形成了我们细胞的复杂机制。信息流，也被称为基因表达，在多个步骤中受到调节，以产生不同类型的细胞，如脑细胞和肌肉细胞。此外，当基因表达控制机制出错时，可能会出现癌症和神经疾病等多种疾病。因此，详细了解基因表达是如何控制的，对于抗击疾病和提供对不同类型的细胞如何从较不专门的祖细胞分化出来的基本了解是重要的。卡拉科博士的研究项目将更深入地理解几个特定的基因表达层如何促进被称为神经元的脑细胞的生长、分化和功能。具体地说，他的团队将研究信使RNA生产和成熟的共转录和转录后步骤中的控制机制。他的实验室将以秀丽线虫作为一个易于处理的模型系统，1)通过基因筛选方法确定组织和单个神经细胞中信使RNA处理事件的控制因素；2)使用高通量测序方法确定基因组序列变化对mRNA处理调控的影响；3)使用高通量遗传相互作用筛选来确定导致动物行为和神经元功能缺陷的RNA结合蛋白的组合作用；以及4)使用荧光显微镜创建单个神经元分辨率下的RNA结合蛋白亚细胞定位图谱。这些目标将为基因表达的关键步骤如何影响神经系统的发育和功能提供基本的机制洞察。卡拉科博士的研究项目还将对再生医学和疾病研究产生影响，通过识别分子“参与者”来协调脑细胞如何产生和维持，以及最终这些细胞如何在疾病中出现故障。

Genetic information from our DNA is transcribed to messenger RNA and then translated to produce proteins, the latter forming the complex machinery of our cells. The flow of information, also called gene expression, is regulated at multiple steps to produce diverse cell types, such as brain cells and muscle cells. Moreover, numerous illnesses such as cancer and neurological disorders can arise when gene expression control mechanisms go awry. Thus, a detailed understanding of how gene expression is controlled is important to combat disease and provide a basic understanding of how different cell types emerge from less specialized progenitor cells. Dr. Calarco's research program will develop a deeper understanding of how several specific layers of gene expression contribute to the growth, differentiation, and function of brain cells called neurons. Specifically, his group will study control mechanisms that occur at the co- and post-transcriptional steps of messenger RNA production and maturation. Using the roundworm Caenorhabditis elegans as a tractable model system, his lab will 1) identify factors controlling messenger RNA processing events in tissues and individual neuronal cell types using genetic screening approaches; 2) use high-throughput sequencing-based approaches to determine the impact of genome sequence variation on mRNA processing regulation; 3) use high-throughput genetic interaction screens to identify combinatorial interactions of RNA binding proteins that lead to defects in animal behaviour and neuronal function; and 4) Use fluorescence microscopy to create an atlas of RNA binding protein subcellular localization patterns at single neuron resolution. These objectives will provide fundamental mechanistic insight into how key steps of gene expression impact nervous system development and function. Dr. Calarco's research program will also have implications in regenerative medicine and studying disease by identifying the molecular "players" that orchestrate how cells of the brain are created and maintained, and ultimately how they can malfunction in disease.