RNA polymerase II CTD modifications and transcriptional dynamics: noise and cell cycle effects.
Lead Research Organisation:
University of Warwick
Department Name: Warwick Medical School
Abstract
Programme overview:
This MRC-funded doctoral training partnership (DTP) brings together cutting-edge molecular and analytical sciences with innovative computational approaches in data analysis to enable students to address hypothesis-led biomedical research questions. This is a 4-year programme whose first year involves a series of taught modules and two laboratory-based research projects that lead to an MSc in Interdisciplinary Biomedical Research. The first two terms consist of a selection of taught modules that allow students to gain a solid grounding in multidisciplinary science. Students also attend a series of masterclasses led by academic and industry experts in areas of molecular, cellular and tissue dynamics, microbiology and infection, applied biomedical technologies and artificial intelligence and data science. During the third and summer terms students conduct two eleven-week research projects in labs of their choice.
Project:
In biology, each living cell is slightly different to its neighbours through constant variations at a molecular level. These molecular random variations (or biological noise) are currently one of the most important topics in molecular biological research. It has become clear that 'randomness' plays decisive roles in many biological contexts, including clinically important settings such as stem cell differentiation, HIV infections, control of the immune system or cancer.
This topic is also highly relevant in the design of complex artificial gene regulatory networks. Such synthetic biology undertakings hold great promise for many diverse fields, including energy and food production and the enhancement of human health, but are impeded by biological noise. If systems are designed based on more than four or five genes that are supposed to regulate each other's activity, the behaviour of the network becomes very noisy and unpredictable. Means to better understand and control biological noise are thus greatly sought after.
This project aims to identify the molecular causes of a particularly noisy process in the cell called transcription, which is the production of messenger-RNAs. For currently unknown reasons, the rate of this process fluctuates strongly. This gives rise to vastly different messenger-RNA numbers in different cells of the same type. Due to transcription's central importance in biology, it is important to understand the mechanistic origins and effects of transcriptional noise. The enzyme that makes messenger-RNAs from DNA, RNA polymerase II, has a long tail that affects its behaviour. This research will focus on elucidating the role of said tail, with the intention of advancing understanding of the origins of biological fluctuations, and potentially identifying ways to control and/or modulate them. This will yield insights into the molecular causes of diseases and, in the long term, will assist in the development of new generations of treatment strategies.
This MRC-funded doctoral training partnership (DTP) brings together cutting-edge molecular and analytical sciences with innovative computational approaches in data analysis to enable students to address hypothesis-led biomedical research questions. This is a 4-year programme whose first year involves a series of taught modules and two laboratory-based research projects that lead to an MSc in Interdisciplinary Biomedical Research. The first two terms consist of a selection of taught modules that allow students to gain a solid grounding in multidisciplinary science. Students also attend a series of masterclasses led by academic and industry experts in areas of molecular, cellular and tissue dynamics, microbiology and infection, applied biomedical technologies and artificial intelligence and data science. During the third and summer terms students conduct two eleven-week research projects in labs of their choice.
Project:
In biology, each living cell is slightly different to its neighbours through constant variations at a molecular level. These molecular random variations (or biological noise) are currently one of the most important topics in molecular biological research. It has become clear that 'randomness' plays decisive roles in many biological contexts, including clinically important settings such as stem cell differentiation, HIV infections, control of the immune system or cancer.
This topic is also highly relevant in the design of complex artificial gene regulatory networks. Such synthetic biology undertakings hold great promise for many diverse fields, including energy and food production and the enhancement of human health, but are impeded by biological noise. If systems are designed based on more than four or five genes that are supposed to regulate each other's activity, the behaviour of the network becomes very noisy and unpredictable. Means to better understand and control biological noise are thus greatly sought after.
This project aims to identify the molecular causes of a particularly noisy process in the cell called transcription, which is the production of messenger-RNAs. For currently unknown reasons, the rate of this process fluctuates strongly. This gives rise to vastly different messenger-RNA numbers in different cells of the same type. Due to transcription's central importance in biology, it is important to understand the mechanistic origins and effects of transcriptional noise. The enzyme that makes messenger-RNAs from DNA, RNA polymerase II, has a long tail that affects its behaviour. This research will focus on elucidating the role of said tail, with the intention of advancing understanding of the origins of biological fluctuations, and potentially identifying ways to control and/or modulate them. This will yield insights into the molecular causes of diseases and, in the long term, will assist in the development of new generations of treatment strategies.
