Laboratory of Molecular Neuroscience

We are at the Department of Molecular Neuroscience at the UCL Institute of Neurology. From August 2006 to March 2013, we were at the MRC Laboratory of Molecular Biology.

  • UCL lab website
  • UCL research website

  • The primary task of the nervous system is to process and store information, and we study how this is achieved at the level of RNA molecules. The nervous system contains many cell types, which have diverse shapes and are most often highly polarized. Especially in neurons, specific mRNAs are localized to distal compartments such as the axon growth cones or the dendrites, where they are translated into proteins. Each mRNA passes through several regulatory stages, which are controlled by protein-RNA complexes. In addition to the regulated pre-mRNA or mRNA, these complexes include non-coding RNAs (ncRNAs), RNA-binding proteins (RBPs) and other associated proteins.

    We study the structure and function of protein-RNA complexes in the brain. In recent years, we have studied how these complexes regulate alternative splicing, and how aberrant function of protein-RNA complexes contribute to neurologic diseases. Currently we study how the sequence and structure of pre-mRNAs and mRNAs defines the composition and function of the regulatory complexes. Moreover, we study how the composition of these complexes changes in response to cellular signals, such as neuronal synaptic activity or the signals that initiate motor neuron disease.

    We cross the boundaries of experimental and computational biology by employing cellular and molecular biology, high-throughput sequencing and predictive modeling. To fully understand the dynamic nature of protein-RNA complexes, we study them within intact cells using innovative transcriptomic techniques such as iCLIP. As our model system, we use induced pluripotent stem cells from healthy individuals or patients with disease-causing mutations, which we modify with genome editing and differentiate into specific neuronal or glial cell types.

    Specifically, we aim to:

    1) Determine how the structure of protein-RNA complexes instructs their function in neurons.

    2) Understand how protein-RNA complexes respond to neuronal signals, particularly in motor neurons.

    3) Define how mutations that affect the composition of protein-RNA complexes can impact RNA regulation in neurons, and thereby contribute to neurologic diseases.

    As an RNA passes through the cellular regulatory stages, it is like a character from Mozart's Magic Flute, passing through the ordeals of space and time. And here are some of the RNA stories that we have passed through: