The G&E Program is broadly focused on the fundamental genetic, epigenetic, and genomic mechanisms that control cell growth and differentiation, and that cause cancer and other human diseases. From basic science investigations to translational studies, G&E students and faculty are actively engaged in the pursuit of new scientific knowledge that could one day lead to clinical advances. Below are the broad areas of research being performed in G&E Program labs.
- 表观遗传学
- 发育遗传学
- Human Genetics
- Cancer Genetics
- 基因组维护与维修
表观遗传学
Nearly every cell in our body has the exact same genome, yet that DNA blueprint is interpreted differently in specific settings to create many different cell types. How is the same genetic code read so differently to generate this cellular diversity? How do defects in reading the code lead to pathologies?
The answers to these questions are found in the study of epigenetics, which refers to heritable phenotypic changes that are not mediated by changes in DNA sequence but rather by alterations in genome organization.
DNA is highly compacted within the eukaryotic nucleus in the form of chromatin, which is built from repeating units of histone-DNA particles called nucleosomes. Nucleosome placement, density, and higher order folding all impact accessibility of DNA sequences to transcription factors and regulatory proteins, thereby affecting patterns of gene expression.
染色质结构的变化控制在胚胎发生期间和出生后表达哪种水平基因的位置,何时何地。他们还控制了细胞对环境和生理变化的反应。此外,适当的染色质组织对于维持基因组完整性至关重要。
表观遗传异常与细胞身份的丧失,基因组不稳定性,失控的生长和对信号转导途径的异常反应有关,从而导致疾病状态。
G&E计划的教师正在定义表观遗传因素如何影响正常细胞中基因转录,DNA重组,DNA修复和DNA复制,以了解表观遗传异常如何有助于癌症的发展和进展。
Since epigenetic changes are often reversible, our studies provide strong molecular frameworks for the development of new therapies targeting regulators of key epigenetic events such as DNA methylation, histone modifications, or expression of non-coding RNAs.
发育遗传学
值得注意的是,单个细胞(受精卵)将始终形成一个具有分化的组织和器官的个体,并正确放置在体内。在胚胎发生过程中调节这些过程的基因是什么?不同的细胞和组织如何相互作用以形成功能器官和器官系统?突变导致出生缺陷的哪些基因?
These types of questions can be answered by studying developmental genetics, which focuses on genes and genetic pathways that regulate embryological, postnatal, and regenerative processes.
在G&E计划中,许多实验室在模型生物中采用了遗传方法Drosophila,C. elegans,Xenopus, zebrafish, and mouse, to study a variety of developmental processes.
这些过程包括细胞命运和分化,组织之间的电感相互作用,组织形态发生和器官发生以及干细胞生物学和再生。使用这些模型系统的主要强度是这些研究主要是进行的in vivo.
有趣的是,胚胎在发育过程中使用的许多基因也在成年有机体中部署,以调节生理过程,包括稳态,伤口愈合和再生。因此,许多G&E计划实验室利用这些模型系统来研究涉及生理过程的基因,当改变导致模仿人类疾病的病理时。发育研究产生的基础知识为有一天会导致疾病疗法的转化和临床研究提供。beplay苹果手机能用吗
Human Genetics
为什么有些人终生危险性增加for developing cancer or chronic conditions such as cardiovascular and neurodegenerative disease? Is there a genetic explanation for the repeated occurrence of these conditions among members of the same family? What are the genetic variants inherited within families that can be detected and linked to these conditions?
这些问题的答案是在人类遗传学的研究中找到的。人类遗传学研究的主要目标是确定beplay苹果手机能用吗遗传性疾病的分子基础,阐明慢性病的遗传和基因组基础,以及基于分析方法开发计算工具,以鉴定疾病易感性基因座和患有疾病风险的人。
人类遗传学研究涉及利用广泛的技beplay苹果手机能用吗术和知识,包括分子生物学的基本原理,孟德尔遗传学和最新的基因组工具,包括下一代DNA测序和生物信息学。
G&E Program faculty are identifying mutations and genetic variants that provide a molecular explanation of inherited human diseases. Understanding the molecular basis of human genetic diseases can lead to disease prevention and the development of treatments and cures.
Cancer Genetics
癌症是一种遗传疾病。引起癌症的突变改变了基本细胞行为,包括生长,增殖和迁移。您如何确定影响癌症形成和进展的基因?
One way is to use human genetics to identify cancer-causing gene mutations that are inherited. Another way is to correlate genetic lesions found in sporadically occurring tumors. A powerful approach to identify and understand cancer-causing genes is to use model organisms.
In the G&E Program, these model organisms include the fruit fly (Drosophila), the nematode worm (C. elegans), zebrafish, and the mouse. These systems can be used for large-scalein vivo可以设计出鉴定引起癌症基因或致癌基因的候选基因的遗传筛选以创建人类癌症模型。这些强大的遗传系统导致鉴定了调节细胞行为的遗传途径,而细胞行为会导致肿瘤形成和转移。
人类患者和遗传缺陷的家庭有助于我们的研究,并帮助我们的思维信息,因为我们最终希望这种知识可以提供治疗方法。
Genome Maintenance and Repair
基因组不断受到导致DNA损伤的内部和外部力量的挑战。DNA损伤来自两个程序性细胞过程,例如减数分裂交叉和抗体多样性所需的损伤以及自发损伤,例如DNA复制中的误差,造成损伤化学物质的细胞产生,暴露于辐照或存在环境中的化学物质。
Cells have developed many distinct ways to repair DNA damage, but not all DNA damage is properly repaired. Incorrectly repaired DNA damage can lead to genome rearrangements from point mutations to chromosome breaks or loss. Incorrectly repaired DNA can also lead to programmed cell death.
细胞识别,如何应对和正确repair DNA damage? How does improper repair influence genome stability? How does failure to repair lead to programmed cell death? How do cancer cells with genome damage bypass cell death?
Many G&E Program laboratories are uncovering how cells recognize and respond to DNA damage, with an emphasis on the genetic and epigenetic factors involved in these processes. G&E Program labs are defining the protein complexes and enzymatic activities that recognize and repair different types of DNA damage, while discovering signaling pathways induced to impose cell cycle checkpoints, to facilitate DNA repair, and to promote other cellular process such as programmed cell death. Ultimately these discoveries will lead to novel strategies for increasing the vulnerability of cancer cells to specific therapeutic strategies.