Post by Fabian Coscia and Lab

Chronic pain begins in specialized sensory neurons, but we lack the tools to directly observe its molecular drivers at the protein level. In our new study, published in 𝗡𝗮𝘁𝘂𝗿𝗲 𝗖𝗼𝗺𝗺𝘂𝗻𝗶𝗰𝗮𝘁𝗶𝗼𝗻𝘀, we created the first neuronal subset resolved proteomic map of sensory neurons. 𝘖𝘶𝘳 𝘸𝘰𝘳𝘬 𝘣𝘳𝘪𝘯𝘨𝘴 𝘵𝘰𝘨𝘦𝘵𝘩𝘦𝘳 𝘵𝘸𝘰 𝘸𝘰𝘳𝘭𝘥𝘴: ⚡ Functional neuronal phenotyping through 𝗲𝗹𝗲𝗰𝘁𝗿𝗼𝗽𝗵𝘆𝘀𝗶𝗼𝗹𝗼𝗴𝘆 🧬 Phenotype-resolved exploratory proteomics through 𝗱𝗲𝗲𝗽 𝘃𝗶𝘀𝘂𝗮𝗹 𝗽𝗿𝗼𝘁𝗲𝗼𝗺𝗶𝗰𝘀 By combining these approaches, we could first functionally identify specific nociceptor subtypes and then directly determine their proteomes. 𝘈 𝘧𝘦𝘸 𝘩𝘪𝘨𝘩𝘭𝘪𝘨𝘩𝘵𝘴 𝘧𝘳𝘰𝘮 𝘵𝘩𝘦 𝘴𝘵𝘶𝘥𝘺: 🔬 Quantification of >6,000 proteins from phenotypically defined sensory neurons 🔬 Discovery of novel proteomic markers that define neuron subtypes 🔬 Clear evidence for both alignment and divergence between transcriptomes and proteomes 🔬 Sensitivity pushed to analyse just a section of a single cell body! By modeling inflammatory conditions, we could pinpoint proteins that change as nociceptors become sensitized, bringing us closer to understanding how acute signals transition into chronic pain. For example, we identified B3gnt2 as a potential effector of nociceptor sensitization, a potentially druggable candidate protein. 𝘞𝘩𝘢𝘵 𝘦𝘹𝘤𝘪𝘵𝘦𝘴 𝘶𝘴 𝘮𝘰𝘴𝘵 𝘪𝘴 𝘵𝘩𝘦 𝘣𝘳𝘰𝘢𝘥𝘦𝘳 𝘪𝘮𝘱𝘭𝘪𝘤𝘢𝘵𝘪𝘰𝘯: This approach enables us to directly link 𝗰𝗲𝗹𝗹𝘂𝗹𝗮𝗿 𝗳𝘂𝗻𝗰𝘁𝗶𝗼𝗻, 𝗺𝗼𝗹𝗲𝗰𝘂𝗹𝗮𝗿 𝗶𝗱𝗲𝗻𝘁𝗶𝘁𝘆, and 𝘁𝗵𝗲𝗿𝗮𝗽𝗲𝘂𝘁𝗶𝗰 𝗼𝗽𝗽𝗼𝗿𝘁𝘂𝗻𝗶𝘁𝗶𝗲𝘀. Given that the vast majority of drugs target proteins, this kind of high-resolution proteomic insight opens new avenues for both basic neuroscience and drug discovery. Our work is also the 𝗳𝗶𝗿𝘀𝘁 𝗶𝗻𝘀𝘁𝗮𝗻𝗰𝗲 𝗼𝗳 𝗱𝗲𝗲𝗽 𝘃𝗶𝘀𝘂𝗮𝗹 𝗽𝗿𝗼𝘁𝗲𝗼𝗺𝗶𝗰𝘀 𝗮𝗽𝗽𝗹𝗶𝗲𝗱 𝘁𝗼 𝗻𝗲𝘂𝗿𝗼𝘀𝗰𝗶𝗲𝗻𝗰𝗲, opening up exciting paths toward functionally grounded proteomics in the context of neurobiology and neurodegeneration. This study is the result of a fantastic collaboration with the Gary Richard Lewin lab at our Max Delbrück Center, spearheaded by Sampurna Chakrabarti with stellar support from our Anuar M.. We thank all our co-authors for their invaluable contributions, the funding agencies and the fantastic institutional support! Please find more info below 👇 https://lnkd.in/dKNzQRrF https://lnkd.in/diCRFSgC #painresearch #deepvisualproteomics #neuroscience #singlecell #spatialbiology