(6jq) Biomimetic Microelectronic Systems for Deciphering Neurotransmission and Hormone Release

Research Interests:

Biomimetic microelectronic technologies have transformed biomedical research through the development of innovative devices that help to understand complex biological mechanisms, restore a lost biological function, and to treat diseases. All successful technologies that are employed in human medical applications have been designed or influenced by a clear understanding of underlying biological principles. My research to date has focused on creating biomimetic and biohybrid technologies for examining the neurotransmitter release, biosensing, drug delivery, and material synthesis. I am interested in combining my engineering, physical sciences and biology expertise toward examining the mechanism of vesicular exocytosis and its alterations in neurological disorders and diabetes. I aim to understand the molecular determinants that encode the differential rate of exocytosis of synaptic and large dense core vesicles in neuronal and endothelial cells. Specifically, I will focus on dissecting the role of fusion regulatory protein, lipid composition and co-factors in regulating the exocytosis process under both normal and diseased conditions. This will bring important insight into the vesicle fusion process and will allow us to build a coherent mechanistic model. To do so, I propose a reductionist approach comprising of biomimetic lipid membranes on a chip, neuroprosthesis and synthetic and isolated vesicles to recapitulate physiological behavior under reconstituted conditions. These studies will ultimately enable the design of optimized and targeted drugs for several neurological disorders and diabetes.

During my Ph.D., I have developed several technologies, including long wavelength hybrid silicon photodetectors, porous silicon ELISA for point of care diagnostics, hybrid ultra capacitor for energy storage in collaboration with Storedot, Israel, and controlled nanocrystals synthesis. During my research career, I have developed a number of software packages including Raman's microscopy data analysis suite, super-resolution microscopy data analysis, and single vesicle data analysis. In my postdoctoral research career, I worked on the development of methods to form lipid membranes on a chip to study the kinetics of vesicle fusion, in particular, the exquisite speed and control of neurotransmitter release from synaptic vesicles. This pore-spanning lipid bilayer system faithfully recapitulates the cellular architecture under reconstituted conditions and allows for the precision study of the single vesicle fusion kinetics. This technology has established close collaboration with researchers from Yale and UCL, London for projects, including drug screening against membrane proteins, examining membrane transport and cell signaling in conjugation with advanced microscopy techniques. Through rigorous training, I have gained valuable experience in grant writing, mentoring, and teaching and I strongly believe these experiences will allow me to excel as a principal investigator, overseeing my own laboratory and personnel.

Grant Writing Experience

NIH Pathway to Independence Award (Impact Score = 30), EGIDE Travel Grant (2012), EGIDE Travel Grant (2014).

Postdoctoral Project: “Planar asymmetric suspended lipid membranes and single molecule studies for elucidating neurotransmission”

Under the supervision of Prof. James Rothman, Nanobiology Institute, Yale University

PhD Dissertation: “Bio-Inspired Materials and Bio-Hybrid Microsystems”

Under the supervision of Prof. Csilla Gergely, CNRS, Montpellier, France.

Selected Publications:

1. Ramakrishnan SK, Bera M, Coleman J, Krishnakumar SS, Pincet F, and Rothman JE. “Synaptotagmin oligomers are necessary and can be sufficient to form a Ca2+‐sensitive fusion clamp.” FEBS Letters, 2019, 593: 154-162.
2. Heo P, Ramakrishnan SK, Coleman J, Rothman J, Fleury JB, Pincet F. “Highly Reproducible Physiological Asymmetric Membrane with Freely Diffusing Embedded Proteins in a 3D‐Printed Microfluidic Setup.” Small, 2019, 1900725.
3. Ramakrishnan SK,^# Gohlke A,^# Li F, Coleman J, Xu W, Rothman J, Pincet F. “High throughput single vesicle fusion using free-standing membranes and automated analysis.” Langmuir, 2018, 34 (20).
4. Coleman J, Jouannot O, ^#Ramakrishnan SK, ^# Zanetti N, Wang J, Salpietro V, Houlden H, Rothman J, Krishnakumar S. “PRRT2 Regulates Synaptic Fusion by Directly Moderating SNARE Complex Assembly.” Cell Reports, 2018, 22 (3), p820-831.
5. Ramakrishnan SK, Martin M, Cloitre T, Agarwal V, Cusinier F, Gergely C. “Porous silicon microcavities redefine colorimetric ELISA sensitivity for ultrasensitive detection of autoimmune antibodies.” Sensors and Actuators B: Chemical, 2018, 271.
6. Ramakrishnan SK^*, Zhu J, Gergely C. “Organic-Inorganic Interface simulations for new material discoveries.” Wiley Interdisciplinary Reviews: Computational Molecular Science, 7(1), 2017.
7. Papa Z, ^#Ramakrishnan SK, ^# Martin M, Marquez J, Zimanyi L, Toth Z, Gergely C. “Interactions at the silicon-peptide surfaces – Evidence of peptide multilayer assembly.” Langmuir, 2016, 32(28).
8. Ramakrishnan SK, Jebors S, Martin M, Cloitre T, Agarwal V, Mehdi A, Martinez J, Subra G, Gergely C. “Engineered adhesion peptides for improved silicon adsorption.” Langmuir, 2015, 31(43).
9. Ramakrishnan SK, Martin M, Cloitre T, Firlej L, Gergely C. “Design rules for metal binding biomolecules: Understanding of amino acid adsorption on platinum crystallographic facets by density functional theoretical calculations.” Physical Chemistry Chemical Physics, 2015 14;17(6):4193-8.
10. Ramakrishnan SK, Martin M, Cloitre T, Firlej L, Gergely C. “Molecular Mechanism of Selective Binding of Peptides to Silicon Surface.” Journal of Chemical Information and Modeling,2014, 54(7):2117-26.
11. Ramakrishnan SK, Martin M, Cloitre T, Firlej L, Cuisinier FJ, Gergely C. “Insights on the facet specific adsorption of amino acids and peptides towards platinum.” Journal of Chemical Information and Modeling,2013 53 (12), 3273-3279.

Teaching Interests:

Teaching Experience:

During my PhD, I have taught digital image and signal processing course at the graduate level. I helped many students to learn MATLAB programming for image processing. Although, my experience in teaching is limited, I enjoyed the teaching opportunities that I got, and hopefully my students are good at MATLAB and apply the knowledge for diverse scientific problems. With strong training and an academic excellence award in engineering, I am comfortable to teach all core courses in the biological and chemical engineering discipline. I am interested in developing new courses related to molecular biophysics, microfluidics techniques for biological applications, materials for biomedical applications, Neurotechnology and Neurophysiology.

Mentoring Experience:

I possess extensive experience in teaching and mentoring students to perform outstanding research. I have advised the three undergraduate students during my graduate school. During my postdoctoral career, I trained one undergraduate and a graduate student for making suspended lipid membranes. I am currently mentoring a high-school student in computer programming for efficient data analysis. Along with my research, I supervised and advised PhD students and postdocs in my lab to carry out single molecule studies and trained them in microscopy techniques. I am eager to continue an interdisciplinary training programs to students as a junior faculty member.

Teaching Philosophy:

My teaching philosophy is that keep students interested and involved during the class. It is essential to understand the material and correlates with real-world examples. By presenting concepts in the context of practical challenges, they should be able to apply the knowledge for practical applications. In my teaching experience, I have felt that demonstrating the text with examples will help the students remember even when they are out of college. Another essential tool is keeping the classroom interactive by encouraging them to ask questions during the lectures. I tend to avoid lengthy speech by interjecting short, interactive exercises and examples into the lesson. For example, 5-10-minute short conceptual explanation followed with problem-solving exercises. This facilitates the students actively engages in the class and gets instant feedback if they do not understand.