Nimesh
Shukla

Optical Spectroscopist &
Expert in Ultrafast time resolved measurements

Intro

What I am all about.

Hi, my name is Nimesh Shukla and I am an Optical Spectroscopist and Biophysicist with background in Electrical engineering. When I was 4 years old my brother used to tell me stories about how the work of great scientists like Madam Curie, Albert Einstein and Graham Bell changed the world. Since early childhood scientists were my celebrities and I always dreamed to be a scientist one day. This desire pushed me to gain the best possible education I could get.

At the age of seventeen I ranked 4351 out of half a million candidates in the IITJEE exam and got the chance to study at the prestigious Indian Institute of Technology (ISM) Dhanbad in India. Where I completed my B.Tech. degree in Electrical Engineering. Currently I am pursuing PhD in physics under the guidance of Dr. Christina Othon here at Wesleyan University in Middletown CT USA.

Officially, my job here at Wesleyan is to use various optical spectroscopy techniques to study the dynamics of water and its impact on proteins/ write peer reviewed articles/ collaborate with other research groups and train undergraduate researchers. Basically? it’s all about helping biology community to find out the ultimate bio-preservative molecule which could make biological specimens survive at extreme environmental conditions such as from boiling to freezing temperatures, no oxygen or extremely fetal radiation. Extremophile animals in nature such as Tardigrade can already do this. It’s been known that extremophiles use a special disaccharide sugar called trehalose to gain such incredible properties. These sugars act as osmolyte and modify network of water to stabilize protein structures. This property has led to the widespread use of various disaccharide osmolytes in the cosmetic, food, and pharmaceutical industries. In our lab, we use Ultrafast spectroscopy and Nonlinear optics to develop molecular level understanding of dynamics of water around various osmolytes and study its impact on biomolecules. We recently demonstrated that a slowdown of as low as 10% in dynamics of water could impact protein structures.

In my free time, I love traveling. I am a small-town boy from India who always wanted to see the world, meet new people, learn more about their work and their life. I desperately await moments of free time and whenever I get a chance I drive and I drive for hundreds of miles. Check out the places I drove by myself after coming to USA here. I also love cooking; my friends always compliment me that, after their mom I cooked the most delicious meal(😊). I love playing chess and sudoku. It helps me improve concentration and build memory. My highest rating on chess.com was 1697. Check out my chess.com profile here. I also enjoy regular running, cycling and hiking. This helps me to stay healthy and focused, strongly needed to be on top of my game.

I am currently looking for exciting and challenging opportunities which could provide me a platform to fulfill my childhood dream of contributing something significant to this world. I am strongly interested in new disruptive innovations/ technological integration in a collaborative, team oriented and interdisciplinary environment.

Ultrafast up-conversion,TCSPC, Nonlinear optics (SFG,SHG,THG) 100%
Fluorescence spectroscopy/microscopy, CD, SLS, ITC 100%
IEX, SDS-PAGE, protein purification, SDS-PAGE 95%
Molecular simulations (Autodock VINA, Gaussian, LAMMPS) 95%
Programing (MATLAB/SIMULINK, LabVIEW, Origin)90%
Programing (C, Python, Batch/Shell scripting, HTML/Web Design)75%

Experience

Expertise in Biophysics/Biochemistry and Physical chemistry, Computational Modeling, Optics,Specroscopy,

Spectroscopy

During my graduate research I built an optical spectroscopy lab from scratch. This lab includes multiple spectroscopic techniques such as Femtosecond fluorescence up-conversion, TCSPC, UV/VIS, CD Spectroscopy and Static light scattering.

Optics &
Optoelectronics

Strong knowledge of optics used in various spectroscopy/microscopy techniques.
Optical Components: Lasers (Ultrafast Pulse/CW), Lenses & Mirrors (plane/parabolic/Dichroic, UV/VIS/IR), Diffraction Grating/Monochromators, Polarizer and waveplates
Optoelectronics: Photon counter, Lock-in Amplifier, Gated integrator, PMT and Photodiodes, Ultrafast Pulse Picker, DC and AC circuits using linear transistors, Integrated circuits and Digital integrated circuits

Physical chemistry and Biophysics

Expertise in interactions of proteins with water and various osmolytes. Authored and published multiple peer reviewed articles in biophysics/biochemistry/physical chemistry journals. Helped prepare manuscript reviews for the Journal of Physical Chemistry, Physical Chemistry Chemical Physics (PCCP) and Food Research International. Hands on experience of multiple biophysical techniques including ITC, CD, UV/VIS,IEX, SLS,SDS-PAGE, protein purification, SDS-PAGE, Fluorescence spectroscopy and Ultrafast upconversion. Extremely familiar with and strong fundamental understanding of HPLC, RP-HPLC.

Computational Modeling

Performed DFT calculations and MD simulations using Gaussian, Autodock VINA and LAMMPS on a high-performance computing cluster.
Expertise in LabVIEW, MATLAB and Origin. Experience of C,Python, Batch/Shell scripting, HTML/Web design.

Works

Check out the fluorescence upconversion experimental design and my current/past projects. Click on image to see detail

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Optical Spectroscopy Lab

Capable of measuring dynamic processes ranging from 50fs to few seconds

I single handedly designed, built and maintained multiple fluorescence spectroscopic experimental designs from scratch. I mounted every single piece of optics, performed laser alignment, installed all the optoelectronics and wrote programs to communicate with electronics ( Check out few scripts that I have written here.). From this project, I have acquired deep knowledge of optics and electronics required for designing/troubleshooting optical spectroscopy/microscopy instruments.

Check out the schematic diagram shown below for fluorescence upconversion experimental design that I built in my lab.

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Adviser: Christina Othon

Year: 2013-2017

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Retardation of Bulk Water Dynamics by Disaccharide Osmolytes

Modification of hydration dynamics and its impact on protein structure

This study compares the hydration of small probe solutes in various low concentrations of trehalose and sucrose. We use fluorescence frequency up-conversion to measure the relaxation of water around the excited state of two fluorophores: the dye molecule Lucifer yellow ethylenediamine (LYen) and the naturally fluorescent amino acid tryptophan. Read the abstract below from the article we published in Journal of Physical Chemistry B in 2016.

Our results indicate a reduction in bulk water reorganization rate of approximately 30%. We observe this retardation in the low concentration regime measured at 0.1 and 0.25 M, far below the onset of glassy dynamics. This reduction in water activity could be significant in crowded biological systems, contributing to global change in protein energy landscape, resulting in a significant enhancement of protein stability under environmental stress. Download the full article from here

Representative abstract for this project.

Project Leader: Christina Othon

Year Published 2016

Journal Journal of Physical Chemistry B

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Sucralose Destabilization of Protein Structure

Demonstrated for the first time that sucralose (splenda) is destabilizing in nature for protein structures

This project was selected for APS march meeting press conference and Webcast in 2015. Watch professor Othon presenting this work at approx. 34 min mark here

ABSTRACT: Sucralose is a commonly employed artificial sweetener that behaves very differently than its natural disaccharide counterpart, sucrose, in terms of its interaction with biomolecules. The presence of sucralose in solution is found to destabilize the native structure of two model protein systems: the globular protein bovine serum albumin and an enzyme staphylococcal nuclease. The melting temperature of these proteins decreases as a linear function of sucralose concentration. We correlate this destabilization to the increased polarity of the molecule. The strongly polar nature is manifested as a large dielectric friction exerted on the excited-state rotational diffusion of tryptophan using time-resolved fluorescence anisotropy.

Check out the melting point of BSA and SNase in presence of Sucralose

Download the full article from here

Project Leader: Christina Othon

Year Published 2015

Journal Journal of Physical Chemistry Letters

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Sucralose interaction of protein structure

Developed molecular level understanding on interaction of sucralose using various computational and experimental methods

In this study, we explored the effect of sucralose on bulk hydration dynamics and its impact on stability of proteins. We also explored the interaction of sucralose with four model protein systems using docking simulations and discussed its implication upon preferential exclusion mechanism of biopreservation.
We accomplished this by using a combination of ultrafast optical spectroscopy and computational analysis on a variety of model systems.

This work is currently under review at Archives of Biochemistry and Biophysics, unpublished article can be downloaded here.

Adviser: Christina Othon

Year: 2017

Journal: ABB

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2D Broadband upconversion

Capable of measuring time resolved emission spectra(TRES) without reconstruction

I worked on this experiment while I visited EPFL Lausanne in Switzerland as visiting researcher in the summer of 2014. This is a very powerful technique which require excitation of fluorophore at multiple wavelengths and the emission spectrum was dispersed through a grating and then recorded directly through a CCD camera. Excitation pulses 70 fs pulse width and a repetition rate of 130 kHz are generated from sum frequency mixing in a nonlinear optical parametric amplifier (NOPA).
As a visiting researcher at EPFL Switzerland, I gained expertise in Pulse shaping, Parametric amplification, and 2D Broadband upconversion spectroscopy and completed a project on measurement of hydration dynamics within two months.

Download the publications resulted from this project here and here

Project Leader: Majed Chergui

Year June 2014

PUBLICATIONS

Publications/conference presentations

PUBLICATIONS:

Shukla N, Pomarico E, Chen L, Chergui M, Othon CM. 2016. Retardation of Bulk Water Dynamics by Disaccharide Osmolytes. Journal of Physical Chemistry B 120 (35) 9477-9483

Chen L, Shukla N, Cho I, Cohn E, Taylor EA, Othon CM. 2015. Sucralose Destabilization of Protein Structure. Journal of Physical Chemistry Letters 6 (8) 1441-1446

Shukla N, Pomarico E, Taylor EA, Cody Hecht, Chergui M, Othon CM. “Sucralose Interaction with Protein Structure”, under review at Archives of Biochemistry and Biophysics.

CONFERENCE PRESENTATIONS:

Shukla N, L. Chen, Pomarico E,Chergui M, Othon CM. Retardation of Hydration Dynamics in the Bulk by Disaccharide Osmolytes. Oral presentation delivered at American Physical Society Conference, New England Section, Worcester, Massachusetts 2017

Shukla N, L. Chen, Pomarico E,Chergui M, Othon CM. Retardation of Hydration Dynamics in the Bulk by Disaccharide Osmolytes. Oral and Poster presentation delivered at American Physical Society Conference, March Meeting, New Orleans Louisiana, 2017

Shukla N, Pomarico E,Chergui M, Othon CM. Retardation of Hydration Dynamics in the Bulk by Disaccharide Osmolytes. Oral presentation delivered at American Physical Society Conference, New England Section, Norton, Massachusetts 2016

Shukla N, Pomarico E, Chen L, Chergui M, Othon CM. Retardation of Bulk Water Dynamics by Disaccharide Osmolytes. Poster presentation delivered at Biophysics Retreat Wesleyan University, Middletown, Connecticut 2016

Shukla N, Chen L, Cho I, Cohn E, Taylor EA, Othon CM. Sucralose Destabilization of Protein Structure. Poster presentation delivered at Biophysics Retreat Wesleyan University, Middletown, Connecticut 2015

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