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 types of neurons and glia, which are highly polarized, with diverse shapes and distinct cellular compartments. Messenger RNA (mRNA) carries the genetic information from DNA to the machinery in our cells that makes the proteins. Often, specific mRNAs need to be localized to distal neuronal compartments, such as the axon growth cone or the dendrites, before they can be translated into proteins. As an mRNA travels through the different cellular compartments, it passes through several regulatory stages. These stages are controlled by RNA-binding proteins (RBPs) and non-coding RNAs (ncRNAs), which assemble on the mRNA into a regulatory ribonucleoprotein complex (RNP). In recent years, we showed how the position of RBP-RNA interaction determines its effects on alternative splicing, characterised the function of several RBPs that are implicated in neurologic diseases, and revealed a mechanism that controls the emergence of new exons from transposable elements.

    We study the structure and function of regulatory RNPs in the brain. Each RNP in the cell has a unique structure, which depends on the sequence-specific interactions between mRNA, RBPs and ncRNAs. Moreover, the RNP structure is highly dynamic, since its composition can change in response to cellular signals, such as the signals that may initiate neurodegenerative diseases. To fully understand the dynamic nature of RNPs, we study them within intact cells using innovative genomic techniques. We developed iCLIP, which we now use to study RNPs in brain tissue or in pluripotent stem cells that are differentiated into specific neuronal or glial cell types. We integrate genomic, biochemical and computational techniques to uncover the importance of RNP structure for neuronal biology and neurologic diseases. Specifically, we aim to:

    1) Determine how the structure of regulatory RNPs instructs their function in brain development and disease.

    2) Understand how regulatory RNPs respond to cellular signals, in particular the signals that affect neurons during the initial stages of neurodegenerative diseases, with the primary focus on motor neuron disease.

    3) Define how mutations can either drive evolution of mammalian brain, or cause neurologic diseases, by modifying the regulatory RNPs.

    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: