Our main goal is to understand how connectivity in the nervous system (NS) is established and repaired.
To this end, we study axon growth and guidance, both during development and regeneration, focusing on mechanisms of local mRNA translation. Defective local mRNA translation is implicated in numerous neurodevelopmental disorders, as well as in the limited capacity of the adult central NS (CNS) to regenerate. We are interested in the molecular repertoire of axons, its regulation via local translation during guidance and regeneration, and how its manipulation can modulate axonal behavior.
Axonal Local Translation
Although evidence for axonal protein synthesis in mammals dates back to the 1960s, surprisingly little is known so far about the process. Our previous research uncovered a novel mechanism regulating local mRNA translation in developing neurons, coupled to a formerly undescribed role for actin-associated proteins. More specifically, we identified complexes of the cytoskeleton-associated protein Mena with translational inhibitors and cytosolic mRNAs, and further showed that Mena is necessary for the translational de-repression of certain mRNA transcripts and nascent protein synthesis.
Understanding developing axons
Studying axon development and the regulation of local translation during guidance and synapse formation,
we aspire to understand:
What are the similarities and differences of local translation regulation downstream of different axon guidance signals?
Are the regulatory mechanisms that function during guidance similar to the ones that contribute to synapse formation?
How is the regulation of local translation tuned in different types of axons?
Can we modulate axonal behavior by manipulating local translation?
Understanding adult axon biology
"Once development was ended, the fonts of growth and regeneration of the axons and dendrites dried up irrevocably. In adult centers, the nerve paths are something fixed and immutable: everything may die, nothing may be regenerated. It is for the science of the future to change, if possible, this harsh decree".
Santiago Ramon y Cajal, 1913
Studying the regulation of local translation in adult axons
and its role during axon regeneration,
we aspire to understand:
What are the similarities and differences of local translation regulation in developing and adult axons?
How is the regulation of local translation tuned in different types of adult axons?
The regenerative process of axons is quite similar to their physiological development.
Are the regulatory mechanisms that function during axon development conserved during axon regeneration?
How is the ability of adult axons for local translation contributing to their regeneration after injury?
Can we modulate the capacity of axons for regeneration by manipulating their local translation abilities?