Astrocyte-mediated influences on neuronal dysfunction in human iPSC-based ALS models
Lead Research Organisation:
University of Cambridge
Department Name: Clinical Neurosciences
Abstract
This project is aimed at validating key regulators in astrocyte-mediated degeneration or repair in neuronal insults using
human iPSC-based 3D astrocyte-neuron co-culture systems. A specific question I would address is whether reversal of
primary astrocytic pathological processes (e.g. upregulation of PHLDA3) can delay neuronal pathology in iPSC models of
amyotrophic lateral sclerosis (ALS). The project is based on recent published findings of the Lakatos laboratory (Tyzack
et al., 2017, Nature communications), and I will learn and use in vitro gene-editing methods to modify astrocytic gene
expression to examine its effect on early features of neuronal ALS pathology, such as ER stress. The characterization of
neuronal dysfunction will be also assisted by my access to cell type specific transciptomic data produced in the lab. Both
the experimental platform and vectors will be available for me to optimize the feasibility of my relatively short MPhil
project. I anticipate that I will obtain experience in cutting-edge cell and molecular biology tools and will contribute to
pathomechanistic discoveries relevant to ALS.
human iPSC-based 3D astrocyte-neuron co-culture systems. A specific question I would address is whether reversal of
primary astrocytic pathological processes (e.g. upregulation of PHLDA3) can delay neuronal pathology in iPSC models of
amyotrophic lateral sclerosis (ALS). The project is based on recent published findings of the Lakatos laboratory (Tyzack
et al., 2017, Nature communications), and I will learn and use in vitro gene-editing methods to modify astrocytic gene
expression to examine its effect on early features of neuronal ALS pathology, such as ER stress. The characterization of
neuronal dysfunction will be also assisted by my access to cell type specific transciptomic data produced in the lab. Both
the experimental platform and vectors will be available for me to optimize the feasibility of my relatively short MPhil
project. I anticipate that I will obtain experience in cutting-edge cell and molecular biology tools and will contribute to
pathomechanistic discoveries relevant to ALS.
