权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

Dynamic modelling of synthetically lethal pathways to enable the development of cancer therapeutics

综合致死途径的动态建模以促进癌症疗法的开发

基本信息

批准号：
2618430
负责人：
金额：
--
依托单位：
University of Sussex
依托单位国家：
英国
项目类别：
Studentship
财政年份：
2021
资助国家：
英国
起止时间：
2021 至无数据
项目状态：
未结题

来源：
https://gtr.ukri.org/projects?ref=studentship-2618430
关键词：
Dynamic modelling synthetically lethal pathways

项目摘要

In many cancers the majority of genetic changes that drive the disease involve loss of function of the affected genes.This provides a challenge for targeted therapies that take advantage of the distinctive genetic attributes of cancer cells. Synthetic lethality (SL) is the phenomenon where loss of function in two genes causes cell death, whereas loss of function in either of these genes alone can be tolerated by the cell. Synthetic lethality provides a therapeutic approach that enables tumour suppressor cancer related genes to be targeted pharmacologically.The PhD Student will join the Pearl Bioinformatics Lab who have recently published computational methods that reveal existing SL gene pairs within the human genome and have proposed and validated novel therapeutic SL gene pairs. The project involves identifying a pathway for a therapeutic synthetic lethal gene pair and building dynamic computational models for that pathway. The student will then have the opportunity to optimise and test the model with the industrial partner Oppilotech.In the final year, experimental validation of the target will take place in the Hochegger laboratory in the Genome Damage Stability Centre at Sussex where the student will be trained in experimental methods (e.g. CRISPR/Cas9).We expect this project to have high impact. It will validate computational methodologies to inform biology. Findings will be published in peer reviewed journals. The project has the potential to lead into a drug discovery project within oncology at Oppliotech and ultimately impact on human health.

在许多癌症中，导致疾病的大多数基因变化涉及受影响基因的功能丧失。这为利用癌细胞独特的基因属性进行靶向治疗提供了挑战。合成致死性(SL)是两个基因的功能丧失导致细胞死亡，而这两个基因中的任何一个基因的功能丧失可以被细胞耐受的现象。合成致命性提供了一种治疗方法，使肿瘤抑制和癌症相关的基因能够以药理学为靶点。博士生将加入珍珠生物信息学实验室，该实验室最近发表了揭示人类基因组中现有SL基因对的计算方法，并提出并验证了新的治疗性SL基因对。该项目包括确定治疗性合成致死基因对的途径，并为该途径建立动态计算模型。然后，学生将有机会与工业合作伙伴Oppilotech一起优化和测试模型。在最后一年，目标的实验验证将在苏塞克斯基因组损伤稳定中心的Hochegger实验室进行，学生将在那里接受实验方法(例如CRISPR/Cas9)的培训。我们预计该项目将产生很大影响。它将验证向生物学提供信息的计算方法。研究结果将发表在同行评议的期刊上。该项目有可能导致Oppliotech肿瘤学领域的药物发现项目，并最终影响人类健康。