Seminar by Prof. J. Douglas Armstrong
University of Edinburgh (UK)
Proteomics gives us a parts-list for the molecular machinery that underpins cellular functions. The neuronal synapse in the mammalian brain underpins molecular basis of synaptic/neuronal transmission and the subsequent molecular adaptation to neural events that underpin learning and complex behaviours. Proteomic analysis of synapses has described one of the largest and most diverse proteomes known to biology with over 8000 identified protein species [1].
Over the past 20 years we have looked at the molecular composition of synapses by integrating proteomics data from multiple research groups and focusing on reconstructing the molecular landscape from a functional perspective by overlaying data from biological models, disease association and human genetics. We will look at how these data can be curated to provide a molecular overview of the synapse, how these data can be stored and queried and how the large map of components (~ 8000 different proteins) can be subdivided into smaller more manageable structural groups of proteins and how these groups then relate to function and dysfunction [e.g. 2].
Finally we will look at examples where proteomics datasets provide unique insights into disease processes through combining proteomics data, molecular interaction data and genetic trait data [e.g. 3]. While the use-cases will focus on neurons and brain diseases the methods are generic and can be applied to any area of biology [e.g. 4].
References
[1] A unified resource and configurable model of the synapse proteome and its role in disease. https://doi.org/10.1038/s41598-021-88945-7
[2] The proteomes of neurotransmitter receptor complexes form modular networks with distributed functionality underlying plasticity and behaviour. https://doi.org/10.1038/msb4100041
[3] Targeted tandem affinity purification of PSD-95 recovers core postsynaptic complexes and schizophrenia susceptibility proteins. https://doi.org/10.1038/msb.2009.27
[4] Mena regulates the LINC complex to control actin–nuclear lamina associations, trans-nuclear membrane signalling and cancer gene expression. (preprint DOI: 10.1101/2021.08.31.458340)