Biohybrid Cortical Incubator for Synaptic Circuit Repair in Parkinson's Disease - College of Engineering - Purdue University

Project Description

We propose a transparent, two-photon– and ephys-compatible biohybrid "incubator" that grows engineered neurons directly on the brain and bridges them to degenerating circuitry in the cortex and substantia nigra. We will realize a unique microfluidic axon-guidance spheroid implant in which we replace opaque metal with our Parylene-C-supported semi-transparent Au microelectrode arrays (Gonzales et al., Science Advances 2025), creating an optically clear window through which grafted cortical neurons or dopaminergic neurons extend axons into host tissue. Neurons seeded in microfluidic wells channel their axons toward substantia nigra or cortical targets, forming new synapses that we monitor longitudinally. Surface electrodes on the exposed cortex record graft–host synaptic bridging in real time while two-photon imaging resolves single-neuron and circuit integration in vivo. Leveraging our finding that alpha-synuclein aggregation drives early synaptic phosphoproteome and cortical circuit dysfunction (Khan et al., Nature Communications 2024; Datta et al., Nature Communications 2026), we will test whether biohybrid grafts rescue corticostriatal and nigral computation before irreversible cell loss. This platform unifies nanofabrication, in vivo two-photon imaging, and PD synaptic biology to establish the first regenerative, recordable synaptic interface for neurodegeneration.

Start Date

December 2026

Postdoc Qualifications

Experience in microfabrication, microfluidics, experimental testing, circuits and system neuroscience, electrical engineering.

Co-advisors

Krishna Jayant (Purdue BME; School of Engineering) ; kjayant@purdue.edu
Jean-Christophe Rochet (MCMP; School of Pharmacy); jrochet@purdue.edu 

Bibliography

M. Habibi Matin, Shulan Xiao, and Krishna Jayant, “Mild Focal Cooling Decouples Dendrites to Reconfigure Cortical Output” Advanced Science (2026): e20773

Shulan Xiao, Sang Hoon Um, Leopold N. Green, and Krishna Jayant*, “Intracellular neuronal recordings across DNA tiles” Nature Nanotechnology, 2026

Sanket Samal¶, Shulan Xiao¶, Om Kolhe, Hammad F. Khan, Samantha Nelson, Zhiyi Du, Decheng Wang, Tianqi Wang, Won-June Lee1, Mustafa Ahmed1, Chen Yang, Qing Deng, Elizabeth I. Parkinson, Krishna Jayant*, Jianguo Mei* “Blood-Catalyzed n-Doped Polymers for Reversible Optical Neural Control” Science 392 (6793), eadu5500

Daniel L. Gonzales, Hammad F. Khan, Hayagreev V.S. Keri, Saumitra Yadav, Lyle E. Muller, Scott R. Pluta, and Krishna Jayant, “A translaminar spacetime code supports touch-evoked traveling waves,” Science Advances 11, 5, eadr4038, 2025.

Hammad F. Khan, Sayan Dutta, Alicia N. Scott, Shulan Xiao, Saumitra Yadav, Xiaoling Chen, Tamara L. Kinzer-Ursem, Jean-Christophe Rochet, and Krishna Jayant, “Site-specific seeding of Lewy pathology induces distinct pre-motor cellular and dendritic vulnerabilities in the cortex”, Nature Communications, 2024, 15, 10775.