Analysing the chromatin landscape and transcriptome within sox17+ lineages during zebrafish embryonic development.
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:
Stem and progenitor cells give rise to the diverse range of mature cell types making up all tissues and organs in the human body. Endoderm is a particular type of progenitor cell that contributes to liver, pancreas, thyroid and the respiratory and gastrointestinal tracts, all of which are associated with developmental defects, or represent an unmet need for tissue replacement therapies. In order to understand how developmental defects occur, and to devise therapeutic strategies it will be necessary to understand how genes are correctly controlled in the endoderm, leading to appropriate formation of these major organ systems.
The identity and behaviour of cells is controlled by the combination of genes which are active within them. Activation of individual genes is controlled by the accessibility of specific DNA sequences within the genome to the relevant cellular machinery. This project aims to identify, characterize and functionally study the DNA sequences that contribute to gene activity in the endoderm. This will be achieved using a range of quantitative experimental and computational approaches in the model organism zebrafish.
Zebrafish is an excellent model for understanding human development since their genomes and multiple organ systems are highly similar to humans. There are also established methods to manipulate the zebrafish genome to fluorescently label cells of interest, or create mutations. Additionally, zebrafish develop external to the mother and are transparent in early development allowing easy whole organism analysis. I will use existing fluorescent zebrafish to specifically isolate endoderm cells during development and identify DNA sequences controlling gene activity. I will then generate new fluorescent zebrafish lines allowing me to understand when and where the identified DNA sequences control gene activity over developmental time. Finally, I will study how a subset of these DNA sequences control specific genes and organ formation by specifically deleting or inhibiting them in endoderm cells using CRISPR/Cas9 genome editing, and characterizing the developmental consequences.
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:
Stem and progenitor cells give rise to the diverse range of mature cell types making up all tissues and organs in the human body. Endoderm is a particular type of progenitor cell that contributes to liver, pancreas, thyroid and the respiratory and gastrointestinal tracts, all of which are associated with developmental defects, or represent an unmet need for tissue replacement therapies. In order to understand how developmental defects occur, and to devise therapeutic strategies it will be necessary to understand how genes are correctly controlled in the endoderm, leading to appropriate formation of these major organ systems.
The identity and behaviour of cells is controlled by the combination of genes which are active within them. Activation of individual genes is controlled by the accessibility of specific DNA sequences within the genome to the relevant cellular machinery. This project aims to identify, characterize and functionally study the DNA sequences that contribute to gene activity in the endoderm. This will be achieved using a range of quantitative experimental and computational approaches in the model organism zebrafish.
Zebrafish is an excellent model for understanding human development since their genomes and multiple organ systems are highly similar to humans. There are also established methods to manipulate the zebrafish genome to fluorescently label cells of interest, or create mutations. Additionally, zebrafish develop external to the mother and are transparent in early development allowing easy whole organism analysis. I will use existing fluorescent zebrafish to specifically isolate endoderm cells during development and identify DNA sequences controlling gene activity. I will then generate new fluorescent zebrafish lines allowing me to understand when and where the identified DNA sequences control gene activity over developmental time. Finally, I will study how a subset of these DNA sequences control specific genes and organ formation by specifically deleting or inhibiting them in endoderm cells using CRISPR/Cas9 genome editing, and characterizing the developmental consequences.
Organisations
Studentship Projects
| Project Reference | Relationship | Related To | Start | End | Student Name |
|---|---|---|---|---|---|
| MR/N014294/1 | 01/10/2016 | 30/09/2025 | |||
| 1789450 | Studentship | MR/N014294/1 | 03/10/2016 | 31/03/2021 | Randa Elsayed |
| Description | helping out with open day for integrated science |
| Form Of Engagement Activity | Participation in an open day or visit at my research institution |
| Part Of Official Scheme? | No |
| Geographic Reach | Regional |
| Primary Audience | Schools |
| Results and Impact | The idea was to get people interested in interdisciplinary science. I gave a talk to participants explaining to them my work and the importance of using science from different disciplines to solve real life problems. I also talked to students to give them a brief overview of the programme, and to answer any questions they may have about the university, life at Warwick, accommodation etc. I was pleased that I managed to convince some people to apply to the programme even though they came for a different programme entirely. |
| Year(s) Of Engagement Activity | 2019 |
| Description | interview for MRC DTP |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Geographic Reach | National |
| Primary Audience | Other audiences |
| Results and Impact | I gave a presentation to about 10 students at the MRC DTP interview. It was a 10 minute non-technical talk of my research project (using zebrafish to study cis-regulatory modules that likely govern endoderm development) with 5 mins of questions. The students became aware of the advantages of using zebrafish to study development but also how they are essential to my research project and future regenerative medicine. Most of the students were not aware of zebrafish and their use as animal models but following the non-technical talk and tour of the zebrafish facility, for which I also provided, they became increasingly interested in understanding more about them. |
| Year(s) Of Engagement Activity | 2018 |
| Description | poster presentation at EdinFish |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Professional Practitioners |
| Results and Impact | I presented my poster to postgraduate students and even group leaders. This sparked questions and discussions. It was extremely helpful as I managed to help a few people out with their projects, but also I given a few suggestions to make my presentation more engaging. I now use these tips on every presentation that I give |
| Year(s) Of Engagement Activity | 2017,2019 |
| Description | presentation at Crick-Beddington symposium |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Professional Practitioners |
| Results and Impact | I presented my poster to postgraduate students and even group leaders. This sparked questions and discussions afterwards, and a few suggestions have been made that helped me to express my opinions more clearly |
| Year(s) Of Engagement Activity | 2013,2019 |
| Description | public engagement |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Geographic Reach | Regional |
| Primary Audience | Public/other audiences |
| Results and Impact | my goal was to show people the importance of using zebrafish for studying development. My goal was to show them some zebrafish embryos and then explain what I use them for and how we can use them to study different genes associated with organs such as the liver and pancreas. I engaged with people who either lack science knowledge or have very basic understanding of biology and explained in a way that makes it very simple for them to understand |
| Year(s) Of Engagement Activity | 2020 |
| Description | short talk during open day |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Geographic Reach | Regional |
| Primary Audience | Schools |
| Results and Impact | I gave a brief presentation of my project to young school students who are looking to come to Warwick to study an undergraduate degree. I gave them a brief introduction to my past experiences, and what led me to do a PhD. Finally, I talked about the use of coding and therefore, the importance of interdisciplinary work for my project. |
| Year(s) Of Engagement Activity | 2019 |