Neuronal RNA Biology

来自我们DNA的遗传信息被转录成信使RNA，然后被翻译成蛋白质，后者形成了我们细胞的复杂机制。信息流，也称为基因表达，在多个步骤中受到调节，以产生不同的细胞类型，如脑细胞和肌肉细胞。此外，当基因表达控制机制出错时，许多疾病，如癌症和神经系统疾病可能会出现。因此，详细了解基因表达是如何控制的，对于对抗疾病非常重要，并提供了对不同细胞类型如何从不太专业的祖细胞中出现的基本理解。Calarco博士的研究计划将更深入地了解基因表达的几个特定层如何促进称为神经元的脑细胞的生长，分化和功能。具体来说，他的团队将研究发生在信使RNA产生和成熟的共转录和转录后步骤的控制机制。利用线虫秀丽隐杆线虫作为一个易于处理的模型系统，他的实验室将1）使用遗传筛选方法确定控制组织和单个神经元细胞类型中信使RNA加工事件的因素; 2）使用高通量测序方法确定基因组序列变异对mRNA加工调控的影响; 3）使用高通量遗传相互作用筛选来鉴定导致动物行为和神经元功能缺陷的RNA结合蛋白的组合相互作用;和4）使用荧光显微镜以单个神经元分辨率创建RNA结合蛋白亚细胞定位模式的图谱。这些目标将为基因表达的关键步骤如何影响神经系统发育和功能提供基本的机制见解。Calarco博士的研究计划也将对再生医学和疾病研究产生影响，方法是确定那些协调大脑细胞如何产生和维持的分子“参与者”，以及最终它们如何在疾病中发生故障。

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.