Use of a cell-line (A1ATD) in metabolism and pathogen research
Research type
Research Study
Full title
Use of a patient-derived cell-line (A1ATD) in pathogen research and for modelling metabolic disorders at the Wellcome Trust Sanger Institute
IRAS ID
182429
Contact name
Subhankar Mukhopadhyay
Contact email
Duration of Study in the UK
5 years, 0 months, 2 days
Research summary
iPSCs (induced Pluripotent Stem Cells) mimic stem cells as they are able to divide and maintain themselves indefinitely but also have the potential to differentiate i.e., develop from one cell type to another, more specialised, type (pluripotency).
The A1ATD iPSC line was derived from a patient suffering from hepatic disease as a result of a DNA change (genetic mutation). The A1ATD (corrected) line has had this mutation 'corrected' to normal in the laboratory.
In brief, this study broadly seeks to characterise and compare the A1ATD and A1ATD (corrected) lines, alter the genetic make-up of these cell-lines, create new cell-lines, differentiate cells into different cell types, such as, immune cells and organoids ('organoids' are clusters of cells), and examine any changes in susceptibility to infection and the immune response.
The study will use a variety of assays, including genetic alteration through targeted mutations (changes in the DNA) in specific genes or deletion of whole genes; differentiation (changing from one cell type to another) of A1ATD, A1ATD (corrected) and any new mutated A1ATD lines; and we will create organoid cell-lines in order to investigate how the mutations affect susceptibility and response to infection.
Some of these newly created differentiated cells, cell-lines and organoids will be challenged with bacteria in order to investigate their ability to respond to bacterial infection. They will also be used to screen existing and novel anti-microbial and anti-inflammatory agents for potential future therapies.
REC name
London - Riverside Research Ethics Committee
REC reference
15/LO/1126
Date of REC Opinion
16 Jun 2015
REC opinion
Favourable Opinion