(6jo) Using Microrobotic Tools for Probing Cellular Pattern Generation and Morphogenesis

Research Interests: Fate specification and differentiation of embryos during development is controlled by concentration gradients of morphogens. Most of these gradients are formed through diffusion of the signaling molecule from a localized source and can be described by a reaction diffusion equation with production and degradation terms. It is less clear, however, how subcellular processes lead to the observed gradient shapes. It has been shown that morphogen interactions with surface receptors or inhibitors with different diffusion rates affect gradient shape. As well, temporal variations in gradient amplitudes during pattern formation have been observed. Current methods in literature rely on static one-and-done patterns to study tissue-level gradient shapes, which are not sufficient to map the kinetics of pattern formation. Thus, there are significant theoretical and technical gaps to overcome if we are to determine how dynamic gradient behavior governs cell fate downstream. My goal is to use microrobotic systems to delivers signaling molecules to a network of engineered cells to generate user defined patterns with spatial and temporal control. This will help us to understand how single cells communicate in space and time to generate organs and to harness this knowledge to develop organoids. Using genetic technology and synthetic biology, and armed with the better control over cell differentiation, I will endeavor to create high fidelity 3D tissues from engineered stem cells.

An exciting avenue for further study is cell polarization. Asymmetric cell division generates two functionally different daughter cells with distinct fates because of the unequal distribution of cell fate determinants or signaling pathway components. The molecular mechanisms driving and maintaining asymmetric divisions are poorly understood, but signaling pathways such as Notch and Wnt are known to be key factors. Due to sub micrometer precision in the placement of microparticles using the robotic systems, I would be able to place a morphogen loaded microparticle at a particular position on the cell surface and then monitor cell division and the asymmetric distribution of the proteins in response to different directions of the morphogen source.

1. S. Das, E.B. Steager, M. A. Hsieh, K. Stebe, V. Kumar. 'Modelling and Ensemble Control of Multiple Catalytic Microrobots', Journal of Micro-Bio Robotics, In Press

2. S. Das, E. E. Hunter, 6. E. B. Steager, V. Kumar. 'Controlled Delivery of Signaling Molecules using Magnetic Microrobots', in 2018 International Conference on Manipula- tion, Automation and Robotics at Small Scales (MARSS), IEEE, July 2018, Nagoya, Japan

3. S. Das, E. B. Steager, K. J. Stebe, V. Kumar. 'Simultaneous control of Spherical Microrobots using Catalytic and Magnetic Actuation', in 2017 International Conference
on Manipulation, Automation and Robotics at Small Scales (MARSS), IEEE, July 2017, Montreal, Canada

4. S. Das, O. Shklyaev, A. Altemose, H. Shum, I. Ortiz-Rivera, L.Valdez, T. E. Mallouk, A. Balazs, A. Sen. 'Harnessing Catalytic Pumps for Directional Delivery of Microparticles
in Microchambers', Nature Communications, 8, 14384 (2017)

5. S. Das, A. Garg, A. Campbell, J. Howse, D. Velegol, A. Sen, R. Golestanian, S. Ebbens. 'Boundaries can steer active Janus spheres', Nature Communications, 6, 8999
(2015)

6. W.Duan, W.Wang, S. Das, V. Yadav, T.E. Mallouk, A. Sen. 'Synthetic Nano- and Micromachines in Analytical Chemistry: Sensing, Migration, Capture, Delivery, and Sep-
aration', Annu. Rev. Anal. Chem., 8, 311 (2015)

7. K.K.Dey, S. Das, M. Poyton, S. Sengupta, P. Cremer, P. Butler, A. Sen. 'Chemotactic Separation of Enzymes', ACS Nano, 8, 11941 (2014). Editors Choice

Teaching Interests:

As a child I delighted in competing to learn new things before my peers and in sharing my knowledge with others. I recall being scolded in primary school for teaching my classmates long division! This thirst for knowledge and desire to teach are still major parts of my life, motivating my pursuit of an advanced degree in chemistry in order to become an educator in the sciences. As an adult, I have come to appreciate the influence teachers have on their students. My goal as a teacher would be to challenge my students and inspire them to grow and expand their horizons. I want my students to learn from and mentor each other. I am a big believer in the power of collaboration and collective learning and would like my students to leave my classroom with the collaborative spirit in mind. I also hope to instill in my students the confidence to not know all the answers but the ability to go and find the answers. My desire to challenge and engage my students is not limited to just the classroom. I was a mentor for two first year female graduate students in my fourth year of graduate school. Also in my fourth and fifth year I participated in Research Snapshots; a program where groups of minority and female high school students spend a day under the guidance of a senior graduate student and learn about their research and life as a PhD student. I was a mentor for a group of 7 freshman and sophomore students and my consistent focus during the program was to encourage them to pursue an advanced STEM degree. I also mentored a minority REU (Research Experiences for Undergraduates) student on a daily basis in the summer of 2015. Moreover, I have been mentoring two junior graduate students in my lab on a weekly basis for the past two years on different projects.