No photo of Han-Jou Chen

Han-Jou Chen


Accepting PhD Students

PhD projects

Dimerization and RNA-binding dynamics of TDP-43 during stress responses in neurons.

RNA-binding proteins (RBPs) are known to play an important role in
neurons, where they are involved heavily in maintaining normal cell
function. Mis-behavior of those proteins can be caused by cellular stress
or dysregulation of protein homeostasis, which leads to protein
aggregation with consequent damage to neurons. One such RBP is
TDP-43, which has a high propensity to form aggregates. These
aggregates are observed in neurons of ageing and neurodegenerative
conditions. Under basal conditions, TDP-43 shuttles between nucleus
and cytoplasm transporting its targeted RNA molecules to neuronal
extensions for further processing. When the cells are stressed, TDP-43
brings target RNAs into an organelle called a stress granule where they
are protected from degradation during stress. Stress granules are
dynamic structures that are quickly dissembled when the stress is
resolved. This mechanism ensures a rapid recovery of protein production
for neurons recovering from stress. Several studies have indicated that
interaction with RNA has an impact on the clustering properties of
TDP-43. However, the nature of the TDP-43 cluster and the mechanism
involved in clustering remain largely unclear.
This project will address the following key questions:
• What mechanisms are involved in the basal activity of TDP-43?
• What are the molecular and cellular processes that contribute to
TDP-43 aggregation?
• How do different functional domains of TDP-43 contribute to the
stress response and recovery period?
The student will use wide range of biochemical and biophysical analyses
to characterize TDP-43 solubility, self-association and structural changes
under different conditions. These will be complemented with cell culturebased
studies where the dynamics of TDP-43 protein movement will be
monitored using live-cell imaging. The student will also use primary
neurons and in vivo models to validate the findings.

If you made any changes in Pure these will be visible here soon.

Personal profile

Education/Academic qualification

PhD: Characterisation of novel VAPB mutation in familial ALS, Imperial College London

1 Oct 200630 Jun 2010

Award Date: 1 Dec 2010

MSc in Molecular Medicine: Regulation of cytokine-withdrawal induced apoptotic cell death, National Taiwan University

1 Sept 200330 Jun 2005

Award Date: 30 Jun 2005

Postdoc: Functional and genetic study of pathogenesis mechanisms underlying TDP-43 aggregation in ALS, King's College London

1 May 201131 Jul 2018