SIDB PhD student
Understanding the function and regulation of
local SHANK3 protein synthesis.
Shank3 mRNA is abundantly localized and translated in dendrites- and is indeed preferentially locally translated in dendrites compared to the soma. Therefore, understanding the functional role of its mRNA localization and local protein synthesis, as well as the molecular machinery regulating its local synthesis, is essential for understanding the functional role of SHANK3 plays at the synapse.
We hypothesize that the local protein synthesis of SHANK3 is essential for regulating synaptic plasticity, and its local synaptic synthesis is required for the synaptic remodelling underlying plasticity.
Application deadline: January 26th 2025
To apply: https://sidb.org.uk/phds/donlin-asp-phd-project/
Please reach out with any questions
Project aims:
1. Define the localization pattern for Shank3 mRNA and assess the local synthesis of SHANK3 protein during plasticity.
2. Define the function role of SHANK3 protein synthesis for the manifestation of structural plasticity.
3. Define the proteins regulating SHANK3 translation, and target these to try boosting SHANK3 synthesis as a rescue mechanism for haploinsufficiency.
SHANK3 (protein)
Shank3 (mRNA)
Project aims:
1. Visualize where newly synthesized PSD-95 and ACTB localize at the synapse during plasticity.
2. Manipulate newly synthesized PSD-95 and ACTB and assess their functional role in the structural changes during plasticity.
3. Define the proteins regulating PSD-95 and ACTB translation during plasticity
Psd95 (mRNA)
PSD95 (protein)
Actb (mRNA)
ACTB (protein)
Eastbio PhD student
Elucidating the function and regulation of PSD-95 and ACTB protein synthesis at dendritic spines
This proteomic modulation of synapses allows neurons to strengthen or weaken them, e.g., synaptic plasticity. Synaptic plasticity is critical in learning and memory as its molecular correlate. Much of the proteomic remodelling at excitatory synapses occurs at the postsynaptic density (PSD), regulating the number and organization of receptors critical for neuronal signalling. Postsynaptic density protein (PSD95) is associated with the postsynaptic density (PSD) of excitatory synapses and plays a crucial role in modulating the structure and composition of receptors at the synapse. Co-current with the remodelling of the PSD are structural increases in the size of the synapse, requiring changes and remodelling of the actin cytoskeleton within the synapse. PSD-95 and Beta-actin (ACTB) are among the most highly translated proteins at the synapse.
We hypothesize that PSD-95 and ACTB's local protein synthesis is essential for synaptic plasticity and that alterations in their local synthesis contribute to changes in synaptic function. In this project, a student will have the opportunity to explore this hypothesis.
Application deadline: January 17th 2025
Please reach out with any questions
Wellcome CDA
funded postdoc
Numerous studies in vitro have demonstrated the importance of RNA capture and local translation for various forms of long-term synaptic plasticity; however, little work has explored this phenomenon in complex neuronal circuits. To comprehend the significance and regulation of RNA localization and local protein synthesis in physiological brain function, studying this phenomenon in complex physiologically functional circuits is essential. We're looking to recruit a postdoc to study synaptic RNA capture and local protein synthesis in complex neuronal circuits using in vivo induction of plasticity, RNA-FISH, metabolic labelling, and proteomic approaches.
Projected start date: fall 2025
To apply: application link expected in March 2025
Please reach out with any questions
