Statistical Bioinformatics Seminar: Lo -- Novel alternative splicing in TDP-43 mutant mouse models of ALS

The aim of the statistical bioinformatics seminar is to provide a forum for people 
working within the broad area of computation and statistics and their application 
to various aspects of biology to present their work and showcase their ongoing 
projects. It is intended to foster the exchange of ideas and build potential 
collaborations across multiple disciplines.

The seminars will be held at 1:00 pm on Mondays at the Charles Perkins Centre, 
Seminar Room (Level 3, large meeting room).
The format of the talk is 30~45 minutes plus questions.

’Meet and Greet’ and afternoon tea with the speaker
This year, we will have a chance for further discussion between 
audience members and the seminar speakers in the following hour of 
the seminar (2:00 pm), with some light afternoon tea.

*Monday March 26, 2018*
*1:00 PM Seminar*
*2:00 PM Meet and Greet with the speaker*
*Level 3 Large Meeting Room*
*Charles Perkins Centre*

*Speaker: Kitty Lo (The University of Sydney)*

Title: Novel alternative splicing in TDP-43 mutant mouse models of 
ALS

Abstract: TDP-43 (encoded by TARDBP) is an RNA binding protein 
central in the pathogenesis of the neurodegenerative disorder 
amyotrophic lateral sclerosis (ALS). However, how TARDBP mutations 
trigger pathogenesis remains unknown. Here, we use novel mouse 
mutants carrying point mutations in Tardbp to dissect TDP-43 
function. Interestingly, we find that TDP-43 C-terminal mutations 
lead to a gain of splicing function. Using two different strains 
we are able to separate TDP-43 loss and gain of function effects. 
This new gain-of-function induces a novel category of splicing 
events, here termed skiptic exons, in which skipping of 
constitutive exons occurs, causing expression changes. Our 
findings provide a novel pathogenic mechanism and highlight how 
gain- and loss-of TDP-43 function affect RNA processing 
differently, suggesting they may play roles at different disease 
stages.

About the speaker: Kitty Lo is currently a bioinformatics 
postdoctoral researcher in the Faculty of Science. Prior to this, 
she was at the University College London and the UCL Institute of 
Neurology. She has also worked in a Cambridge based biotechnology 
startup where she developed cancer diagnostic tools using ctDNA. 
Kitty has a PhD in astronomy from the University of Sydney.