(6gi) Engineering Optical Nanomaterials to Probe Brain Chemistry

Unlocking our understanding of neurological function requires methods that can probe chemical activity at the smallest and fastest time scales. The emergence of optical nanomaterials provides a unique toolset to develop multifunctional optical probes to explore neurochemistry at the nanoscale and millisecond timescale where neurotransmission occurs. I am interested in exploring new methods to engineer hybrid nanomaterials that incorporate covalent and non-covalent attachment of small molecules and polymers to develop fluorescent chemical sensors to probe biological systems.

My recent work focuses on using infrared-fluorescent nanosensors composed of single-walled carbon nanotubes to image the release and re-uptake of dopamine in brain tissue. Dopamine is a neuromodulatory neurotransmitter involved in neural circuits controlling motion, learning, and motivation. Understanding the role of dopamine as a neuromodulator, and the role its dysregulation plays in disease, remains elusive in neuroscience and psychiatric medicine. With custom-built infrared microscopy and spectroscopy equipment I designed (Del Bonis-O’Donnell et al. Adv. Funct. Mater. 2017), and neuromodulator nanosensor technology I developed (Beyene et al. bioRxiv, 2018; Del Bonis-O’Donnell et al. ACS Chem Neurosci. 2018), I have created a platform to image dopamine, and other catecholamines, with unprecedented spatial and temporal resolution required to study endogenous neuromodulation. This approach promises to enable non-invasive, in vivo imaging of neurochemistry deep in the living brain.

My future independent work aims to combine my nanosensor and imaging techniques to probe fundamental biological questions related to neurotransmission. Specifically, the merger of nanosensors with deep-tissue infrared imaging promises to reveal new details into the mechanisms of neurochemical dysregulation involved in neurodegenerative diseases, such as Parkinson’s disease (DoD PRP Young Investigator Award, Awarded 2018). Towards this goal, I will construct microscopy systems that will enable the cooperative use of infrared neuromodulator nanosensors with existing tools for neuroimaging, including calcium imaging and optogenetic stimulation, to create a new ‘neurochemical dimension’ in our neuroscience interrogative toolkit to address the unknowns of brain function.

Additionally, I am enthusiastic to explore new directions in nanomaterial functionalization to create new optical probes for biosensing. Borrowing strategies from combinatorial chemistry, molecular biology, and biomaterials, I will expand the toolkit for biochemical sensing using both carbon nanomaterials and noble metal nanoclusters to visualize the dynamics of new biochemical targets critical to biological function, including additional neurotransmitters, hormones and regulatory proteins.

Select References:

1. JT Del Bonis-O’Donnell, et al. Dual Near-Infrared Two-Photon Microscopy for Deep-Tissue Dopamine Nanosensor Imaging, Funct. Mater., 2017, 27, 1702112.
2. JT Del Bonis-O’Donnell et al. DNA-Stabilized Silver Nanoclusters as Specific, Ratiometric Fluorescent Dopamine Sensors. ACS Chem. Neurosci., 2018, acschemneuro.7b00444.
3. A Beyene, K Delevich, JT Del Bonis-O’Donnell et al. Imaging Striatal Dopamine Release Using a Non-Genetically Encoded Near-Infrared Fluorescent Catecholamine Nanosensor. BioRxiv, 2018.

Teaching Interests:

I am excited to teach topics including transport, thermodynamics, statistical mechanics, and biophysics, with a personal emphasis on integrating hands-on, discovery-based laboratory curriculum with a foundational theoretical background that can be translated to the lecture hall. I intend to leverage my academic background (B.S. Mathematics-Physics, Ph.D. Mechanical Engineering with emphasis in thermofluids and microelectromechanical systems, Postdoc in Chemical and Biomolecular Engineering) and previous experience as a mentor both in the classroom and in the laboratory to provide guidance for undergraduate and graduate students to grow into independent thinkers, scientists and engineers. Previous experience working in laboratory settings comprised of diverse technical and cultural backgrounds will aid me in growing and managing a research group that excels at tackling interdisciplinary problems at the intersections of engineering, physics, chemistry and biology.