About Kaamini
- Advisor: Arnab Mukherjee
- Department: Chemical Engineering
- Campus: UCSB
- BioPACIFIC MIP Research: SET 1 - Bioderived Materials; SET 3 - Functional Biomimics; SET 4 - Degradation-Optimized Materials
What is your research focus?
My overall research interest focuses on designing smart protein-based sensors using molecular engineering and synthetic biology. Currently, I am engineering protein-based calcium sensors, known as CalSens — Calcium-responsive protein-based Sensors, which are detectable in the deep brain using magnetic resonance imaging (MRI). These sensors harness water diffusion and protein degradation to modulate the spin properties of tissue water to generate magnetic signals in response to Ca2+ increase (an established marker of neuronal activity), thereby providing a noninvasive, spatiotemporal measurement of brain activity in living animals. The scientific impact of this technology is in its ability to uncover deep-brain neural circuitry underlying a gamut of biological functions – from memory formation to decision-making – which are largely “invisible” due to the limited penetration depth of optical imaging methods that are currently used to measure neuronal Ca2+ activity. My approach for developing CalSens harnesses aquaporin, a protein derived from plants or yeast that is crucial in transporting water across the cell membrane (bio-derived material). To create CalSens, I propose harnessing and engineering aquaporin’s “cellular plumbing” function (functional biomimicry) to generate a calcium-responsive MRI-readable signal. To make CalSens responsive to changes in neuronal Ca+2, I will use protein engineering to tune aquaporin’s degradation properties to be modulated by changes in Ca2+ levels (degradation-optimized biomaterial). Specifically, an increase in local Ca+2 during neural activity will prevent the degradation of a thermodynamically destabilized CalSens construct, resulting in an MRI-on state. Without neuronal activity, the destabilized CalSens rapidly degrades, leading to an MRI-off state. In this way, CalSens converts neuronal calcium spikes into an MRI signal to enable noninvasive tracking of neural activity at any depth within the brain. In summary, my work represents a new and unorthodox approach to creating noninvasive sensors of brain activity by creating designer proteins that mimic water diffusion to generate MRI signals and engineering their degradation properties to make them responsive to calcium. Integrating biotechnology, protein engineering, and imaging physics, my research aligns well with the broader BioPACIFIC MIP mission and advances bioengineering and bioimaging frontiers.
What excites you about NSF BioPACIFIC MIP?
I believe that becoming a BioPACIFIC MIP Fellow can help me advance my interdisciplinary research which lies at the confluence of biodegradable polymer-based drug delivery, and protein engineering. The major focus of my doctoral thesis centered on polymer-based drug delivery systems for clinical translation. As a postdoctoral researcher, I am developing calcium-responsive smart sensors derived from bio-materials for MRI to facilitate neural mapping. By developing sustainable polymer-based drug delivery platforms, I have gained a solid foundation for developing innovative biomedical solutions that fill translational gaps in drug delivery. As a BioPACIFIC MIP Fellow, I aim to leverage the program's collaborative environment and innovative resources to explore further and integrate sustainable drug release platforms and protein engineering techniques to create novel clinical solutions.
My career goal is to develop clinically translatable, high-performing, sustainable polymer-based drug delivery platforms with tunable degradation profiles, which align perfectly with BioPACIFIC MIP objectives. Using BioPACIFIC MIP's platform to connect and collaborate with experts across disciplines will enable me to achieve my research goals, allowing me to create innovations that address critical challenges in the emerging field of diagnostics and therapeutics (Theranostics). With the support of this dynamic and supportive community, I am confident that I will be able to drive impactful research and inspire the next generation of scientists.
