CIBIO-PhD Colloquia 2016 - Emanuele Buratti

2 December 2016
Versione stampabile

PhD Colloquia 2016

a forum between young researchers and scientists

This is a mini series of 6 seminars given by top experts in different fields covering almost all the area of the PhD program. Each colloquium is a friendly forum where students can learn how to communicate and critically evaluate science. Additionally, it is an opportunity to discuss ongoing research in an informal atmosphere and obtain valuable feedbacks from the experts.
PhD Colloquia bring together young scientists, senior scientists and students in a colloquial setting, encouraging interactions and exchanges of ideas.

The last seminar of the series will take place on December 2nd at 5 pm at room B102 of the Polo Ferraris in Povo2.

Invited speaker: Emanuele Buratti (ICGEB Trieste) 
 

Title: Identification of TDP-43 toxicity modifiers in Drosophila and human neuronal cells

Abstract:

Nuclear factor TDP-43 is a protein involved in a variety of neurodegenerative diseases,
especially in 60% of cases of patients with Frontotemporal Lobar Degeneration (FTLD-
TDP) and almost all cases of Amyotrophic Lateral Sclerosis (ALS). In recent years, many
studies have tried to uncover the pathological events following its aggregation in the
neurons of affected patients.
In general, TDP-43 is an abundant protein within the eukaryotic nucleus that binds to
many coding and non-coding RNAs and influence their processing. Using Drosophila,
we have performed a functional screening to establish the ability of major hnRNP
proteins to affect TDP-43 overexpression/depletion phenotypes. Interestingly, we
observed that lowering hnRNP and TDP-43 expression has a generally harmful effect on
flies locomotor abilities. In parallel, our study has also identified a distinct set of hnRNPs
that is capable of powerfully rescuing TDP-43 toxicity in the fly eye (Hrb27c, CG42458,
Glo and Syp). Most importantly, removing the human orthologs of Hrb27c (DAZAP1) in
human neuronal cell lines can correct several pre-mRNA splicing events altered by TDP-
43 depletion. Moreover, using RNA sequencing analysis we show that DAZAP1 and
TDP-43 can co-regulate an extensive number of neuronal genes that are important for
neuronal survival and synaptic expression. Our results suggest that changes in hnRNP
expression levels can significantly modulate TDP-43 functions and affect pathological
outcomes.

 

Initiative organized by the 29th Cycle PhD students of the PhD Program in Biomolecular Sciences