Prof. Dr. Tommaso Patriarchi

Area of Research

Description of Research Interest

My research centers on engineering and applying genetically encoded tools to reveal how neuromodulatory GPCRs operate within intact circuits. We develop next-generation fluorescent and optogenetic GPCR sensors, including red-shifted and conformational reporters, to monitor endogenous receptor dynamics with high spatial and temporal precision across dopamine, norepinephrine, serotonin, orexin, GLP-1, and related pathways.A key focus is integrating these molecular tools with advanced in vivo imaging and quantitative behavioral paradigms. Using fiber photometry, two-photon microscopy, miniaturized imaging, and circuit-specific manipulations, we map how neuromodulatory signals shape learning, motivation, internal state, and behavioral flexibility.I am particularly interested in collaborations involving protein engineering, GPCR biology, computational design, systems neuroscience, imaging technologies, and models of dysregulated neuromodulation. My group values rigorous methodology, open sharing of reagents, and cross-disciplinary approaches that connect molecular innovation to circuit-level mechanisms and behavior.

Special Expertise

• Engineering of genetically encoded GPCR-based fluorescent and red-shifted biosensors
  
• Protein engineering, directed evolution, and structure-guided design for membrane proteins
  
• In vivo imaging: fiber photometry and miniaturized (mini2P) calcium/neuromodulator imaging
  
• Quantitative behavioral assays linking neuromodulatory dynamics to learning, motivation, and internal-state control
  
• GPCR pharmacology, signaling kinetics, and receptor conformational dynamics
  
• Viral vector design and in vivo delivery (AAV-based expression strategies)
  
• Integrative circuit neuroscience combining molecular tools, electrophysiology, and behavioral analysis
  
• Development and dissemination of open, robust, reproducible molecular tools for neuroscience
  
• Cross-disciplinary project leadership spanning protein design, neuropharmacology, and systems neuroscience
  

Shareable Platforms, Services, Equipment & Infrastructure

• Genetically encoded sensor development pipeline (GPCR-based fluorescent reporters; mutagenesis, screening, validation)
  
• In vivo neural activity monitoring platforms: i) Fiber photometry (multi-color, lifetime-capable); ii) Miniaturized imaging (mini2P) for deep-brain circuit recordings
  
• Advanced protein engineering and molecular biology facilities (directed evolution workflows, cell-based screening, HEK-based assays, neuronal expression systems)
  
• Primary neural culture capabilities (access to UZH PNCF, preparation of cortical/hippocampal neurons, live-cell imaging and transfection workflows)
  
• AAV vector production support (design, cloning, small-scale preparation; access to UZH/ETH viral core for large-scale production)
  
• Behavioral neuroscience infrastructure (automated operant systems, locomotion/anxiety assays, custom paradigms for neuromodulatory studies)
  
• Histology and microscopy suites (confocal, slide scanning, immunohistochemistry workflows)
  
• Expertise-sharing and training in sensor use, imaging, data analysis, viral delivery, and behavioral assay design
  

Member of Collaborative/interdisciplinary Research Consortia

• DEEPER (Deep Imaging Partnership for Neuroscience, EU/Swiss network) – contributor to advanced optical imaging and molecular tool development
  
• European Society for Neurochemistry (ESN) Council – active member involved in scientific programming and community initiatives
  
• UZH / ETH Zurich Core Facility Networks (FGCZ, PNCF, VVF Imaging) – active collaborative user within cross-institutional platforms
  
• UZH Neuroscience Community (ZNZ) – member engaged in interdisciplinary neuroscience research and training programs