The RNA-binding proteins LARP4A and LARP4B promote cell proliferation via distinct subcellular RNA targets and mechanisms
Lead Research Organisation:
King's College London
Department Name: Randall Div of Cell and Molecular Biophy
Abstract
State primary research question and where appropriate the primary hypotheses being tested
We hypothesise that the RBPs LARP4A and LARP4B stabilise and regulate the translation of cancer-related RNA targets in prostate cancer and osteosarcoma cell lines, thereby promoting cell proliferation. The aim of the project is to reveal the mechanisms by which LARP4A and LARP4B function as pro-tumour proteins, specifically elucidating how they regulate the expression of cancer-related genes in prostate cancer and osteosarcoma cell lines.
Proposed plan of work (up to 1000 words)
Please include key aspects of study design, key research methods (including statistical methods and appropriate power calculations for the primary hypotheses. Ensure that it is clear how the design and methods will address the study aims.
Year 1 - we aim to identify how LARP4A and LARP4B regulate the expression of cancer-related genes in prostate cancer and osteosarcoma cell lines. We want to delineate the contributions of their shared key binding partners RNA, PABPC1, and RACK1 in facilitating polyribosome association cancer-related genes. Frac-seq experiments will be done n=5 based on our previous work.
Methodologies: Cell biology, Fraq-seq, molecular biology, microscopy, data analysis
Year 2/3 - The candidates that will be identified from high-throughput data (from year 1) will be functionally validated in cells and in vitro.
We have access to human primary cells that would allow us to test certain biological pathways that may be relevant (e.g. fibroblasts for proliferation, epithelial cells for EMT, blood cells for co-culture assays), and we may also use those.
Methodologies: Cell biology, iCLIP, SLAM-seq, molecular biology, data analysis, microscopy, in vitro biochemistry/biophysics
This information may also be used by the Centre for Doctoral Studies for the electronic submission of Doctoral Training Grants.
We hypothesise that the RBPs LARP4A and LARP4B stabilise and regulate the translation of cancer-related RNA targets in prostate cancer and osteosarcoma cell lines, thereby promoting cell proliferation. The aim of the project is to reveal the mechanisms by which LARP4A and LARP4B function as pro-tumour proteins, specifically elucidating how they regulate the expression of cancer-related genes in prostate cancer and osteosarcoma cell lines.
Proposed plan of work (up to 1000 words)
Please include key aspects of study design, key research methods (including statistical methods and appropriate power calculations for the primary hypotheses. Ensure that it is clear how the design and methods will address the study aims.
Year 1 - we aim to identify how LARP4A and LARP4B regulate the expression of cancer-related genes in prostate cancer and osteosarcoma cell lines. We want to delineate the contributions of their shared key binding partners RNA, PABPC1, and RACK1 in facilitating polyribosome association cancer-related genes. Frac-seq experiments will be done n=5 based on our previous work.
Methodologies: Cell biology, Fraq-seq, molecular biology, microscopy, data analysis
Year 2/3 - The candidates that will be identified from high-throughput data (from year 1) will be functionally validated in cells and in vitro.
We have access to human primary cells that would allow us to test certain biological pathways that may be relevant (e.g. fibroblasts for proliferation, epithelial cells for EMT, blood cells for co-culture assays), and we may also use those.
Methodologies: Cell biology, iCLIP, SLAM-seq, molecular biology, data analysis, microscopy, in vitro biochemistry/biophysics
This information may also be used by the Centre for Doctoral Studies for the electronic submission of Doctoral Training Grants.
Organisations
People |
ORCID iD |
| Maike Henschel (Student) |
Studentship Projects
| Project Reference | Relationship | Related To | Start | End | Student Name |
|---|---|---|---|---|---|
| MR/W006820/1 | 30/09/2022 | 29/09/2030 | |||
| 2886801 | Studentship | MR/W006820/1 | 30/09/2023 | 29/09/2027 | Maike Henschel |