The Role of Epigenetic Stress in Cellular Senescence.
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:
Unlike the majority of mammalian species, the extensive endometrial remodelling that produces a receptive stromal compartment in humans is independent of the presence of an embryo. Instead, it is under maternal endocrine control. This remodelling process is characterised by changes such as influx of uNK cells and differentiation of stromal cells. Collectively these changes are termed decidualization. Recent studies have illustrated that shortly after decidualisation, stromal cells diverge into two distinct sub-populations; one of a senescent phenotype and the other being mature decidual cells capable of forming a nutritive matrix that surrounds an embryo. It is currently unknown how the fate of progenitor cells is decided and how environmental factors could affect the balance of these sub-populations.
In this project, primary stromal cells will be cultured from patient biopsy samples. During their growth period, various molecules capable of mimicking metabolic stress will be added to the cells and their suitability tested using standard biochemical techniques. Decidualization will subsequently be induced through the addition of cAMP and a progesterone derivative. After establishing appropriate stressing conditions, the effect of stress on the senescent and mature sub-populations will be investigated and the origins of this effect studied using the assay for transposase accessible chromatin with sequencing (ATAC-seq).
In conjunction with primary cell culture, fundamental biochemical techniques (Interdisciplinarity - Strategic Skill Priority 2017) such as ELISA, western blotting and cellular senescence assays will be used to evaluate the suitability of various stressing conditions. Analysis of ATAC-seq data additionally will meet Maths, Statistics & Computation criteria (Data Analytics - Strategic Skill Priority 2017 ).
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:
Unlike the majority of mammalian species, the extensive endometrial remodelling that produces a receptive stromal compartment in humans is independent of the presence of an embryo. Instead, it is under maternal endocrine control. This remodelling process is characterised by changes such as influx of uNK cells and differentiation of stromal cells. Collectively these changes are termed decidualization. Recent studies have illustrated that shortly after decidualisation, stromal cells diverge into two distinct sub-populations; one of a senescent phenotype and the other being mature decidual cells capable of forming a nutritive matrix that surrounds an embryo. It is currently unknown how the fate of progenitor cells is decided and how environmental factors could affect the balance of these sub-populations.
In this project, primary stromal cells will be cultured from patient biopsy samples. During their growth period, various molecules capable of mimicking metabolic stress will be added to the cells and their suitability tested using standard biochemical techniques. Decidualization will subsequently be induced through the addition of cAMP and a progesterone derivative. After establishing appropriate stressing conditions, the effect of stress on the senescent and mature sub-populations will be investigated and the origins of this effect studied using the assay for transposase accessible chromatin with sequencing (ATAC-seq).
In conjunction with primary cell culture, fundamental biochemical techniques (Interdisciplinarity - Strategic Skill Priority 2017) such as ELISA, western blotting and cellular senescence assays will be used to evaluate the suitability of various stressing conditions. Analysis of ATAC-seq data additionally will meet Maths, Statistics & Computation criteria (Data Analytics - Strategic Skill Priority 2017 ).
Organisations
People |
ORCID iD |
| Jan Brosens (Primary Supervisor) |
Studentship Projects
| Project Reference | Relationship | Related To | Start | End | Student Name |
|---|---|---|---|---|---|
| MR/N014294/1 | 01/10/2016 | 30/09/2025 | |||
| 1935736 | Studentship | MR/N014294/1 | 02/10/2017 | 30/09/2021 |