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NC3Rs: National Centre for the Replacement Refinement & Reduction of Animals in Research
Fellowship

A computational framework to investigate the mechanical role of the extracellular matrix in tissue development and disease

Dr Nargess Khalilgharibi

At a glance

In progress
Award date
February 2020 - July 2022
Grant amount
£137,927
Principal investigator
Dr Nargess Khalilgharibi
Institute
University College London

R

  • Reduction
  • Replacement
Read the abstract
View the grant profile on GtR

Overview

Why did we fund this fellowship?

This award aims to develop a computational model to study the mechanical role of the extracellular matrix (ECM) in tissue development and function replacing mammalian model organisms, such as rats and mice.

Dysregulated ECM composition, both during early development and later in life, can result in various pathological conditions such as Alport’s syndrome, fibrosis and kidney failure. Animals are used in basic research studies to further understanding of the ECM and to provide insights into disease. The development of the ECM is perturbed in some of these studies, either by genetically modifying the animal to introduce a relevant mutation or by treating the animal with a chemical such as small molecule inhibitors. In vitro methods in ECM research do exist but these require animal-derived matrices, for example Matrigel is often used to provide structural support to 3D organoid cultures used in the research. Dr Nargess Khalilgharibi will build upon work from her supervisor, Dr Yanlan Mao, to develop a computational platform to study the mechanical role of the ECM in shaping and maintaining tissue architecture, helping to replace some rodent studies in this area.

During her Fellowship, Nargess will use this experience to adapt the model to make it applicable to tissues with different structures and properties as well as organoid growth and function. To better enable uptake, Nargess will publish the model with a user-friendly graphical user interface. She will develop skills in quantitative imaging, organoid culture and further expand her computational modelling capabilities.

Impacts

Publications

References

  1. Khalilgharibi N & Mao Y (2021). To form and function: on the role of basement membrane mechanics in tissue development, homeostasis and disease. Open Biology 11(2): 200360 doi: org/10.1098/rsob.200360