In recent years more and more RNA-binding proteins, defects in RNA maturation, and divergent function of RNA machines have been linked to disease. For example, mutations in several ribosomal proteins and ribosome assembly factors cause tissue-specific congenital diseases in humans, and errors in modification and miss-processing were shown to lead to deleterious aggregation of some RNAs. In the lab, we are studying the role of TDP-43 – a key factor in Amyotrophic Lateral Sclerosis (also known as ALS, Lou Gehrig’s disease, or motor neuron disease) –  in translation. We identified that TDP-43 association with translating ribosomes alters their translation output (or Translatome), with increased translation of ALS-linked proteins. This project aims to determine the mechanisms behind this phenomenon: how TDP-43 alters ribosome function and the consequence for ALS development and progression.

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