The overarching theme of the unit is the understanding of synapse biology and the identification of how disease processes impact normal synaptic and brain function. The unit is composed of investigators who develop complementary and convergent approaches to this theme:
1. Ramiro D Almeida is interested in the mechanisms of synapse formation, and in particular in how a delicate balance between local protein synthesis and local protein degradation contributes to appropriate synaptic differentiation (supported by FCT for 2013-2014).
2. Ana Luisa Carvalho is dedicated to studying the cellular and molecular mechanisms of synaptic plasticity, focusing on processes that regulate the postsynaptic composition and the traffic of glutamate receptors (supported by FCT for 2013-15).
3. How changes in protein synthesis and protein degradation contribute to the regulation of the synaptic proteome in BDNF-mediated synaptic plasticity is investigated by Carlos B Duarte. This group also studies molecular mechanisms operating downstream of glutamate receptor overactivation to induce neuronal death in brain ischemia (supported by FCT for 2013-2015).
While these research lines remain a core investment going forward, the unit has been reinforced to address a wider spectrum of questions both at low-level information processing and high-level synaptic circuit function. To implement new lines of research two Assistant Investigators, Paulo Pinheiro and João Peça, have been recruited through the FCT Investigator Program and integrated in the Synapse Biology unit:
4. Paulo Pinheiro works in the leading field of transmitter release mechanisms. Presynaptic vesicle fusion is probably the fastest membrane fusion phenomenon in mammalian cells. Paulo Pinheiro has recently focused on synaptotagmins (syts) and other C2 domain proteins such as Doc2, and he now plans to undertake an integrated approach, from molecular and in vitro to cell physiology and, ultimately, to neuronal networks in the brain, to clarify the possible functions of the different syt isoforms and their interactions with other cellular partners (supported by FCT for 2013-2014).
5. To identify circuit level dysfunctions in neuropsychiatric disorder, João Peça applies top-down approaches focused on optogenetics and the generation of genetically engineered mouse models. Dr. Peça recently established the Shank3 mouse models for autism and described the role of cortico-striatal synaptic circuits in the manifestation of autism-like behavior. A current goal is the identification of the synaptic circuits of social behavior and the study of the synaptic dysfunctions present in autism and schizophrenia. Additionally, having created the first transgenic mice for ChR2, Dr. Peça is also involved in the generation of innovative tools for the neuroscience community. (Support by a Marie Curie CIG, a NARSAD Young Investigator Grant and FCT, for 2013-2016).
The close proximity between the investigators in the unit, the sharing of resources and expertise, and the active recruitment of talented researchers allows the Synapse Biology unit to tackle complex and emerging questions in neuroscience research using multidisciplinary approaches. This working strategy is planned to continue into 2015/2020 with the consolidation of the new Investigators in the Unit and the insertion of new members to reinforce areas of interest. In particular, Ana I Oliveira (who trained with R Yasuda at Duke Univ) has recently been hired to set up a Two-Photon Imaging facility to help address more complex biological questions. We are also actively searching for an investigator to reinforce the study of opposite valence driven behaviors (e.g. appetitive vs aversive), given the role these circuits play in emotional disorders such as depression, anxiety and addiction.
Currently, a total of and 14 PhD holding members and 17 PhD students make up the unit and participate in regular group meetings. Several students are co-supervised by the PIs.