Physics Department Theses and Dissertations

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https://hdl.handle.net/1805/2072

For more information about the Physics graduate programs visit: https://science.indianapolis.iu.edu

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Imaging the Dynamics of Chromatin at Single-Nucleosome Resolution
(2024-12) Iqbal, Mohamed Fadil; Vemuri, Gautam; Liu, Jing; Petrache, Horia; Decca, Ricardo; Wassall, Stephen
DNA is organized into chromatin – a complex polymeric structure which stores information and controls gene expressions. Advancements in microscopy have enabled us to see chromatin in motion – which was previously thought to be static, and these motions contribute to various cellular functions. In my thesis I will demonstrate the molecular tools and biophysical approaches our lab has developed to uncover the mysteries of chromatin dynamics and structures at the single nucleosome resolution; I will also discuss how these new discoveries in chromatin enable us to explore its role in cell functions. This dissertation will first describe the technology advancement of live-cell image analysis; particularly, I will discuss the utilization of AI to improve the spatial and temporal resolution of chromatin imaging. Then I will show complex nature of chromatin where depending on the temporal scale of observation we see a different behavior and how computer simulations can see these differences. Following that, I will introduce our investigation on the role of chromatin motion in DNA damage and repair. Afterwards, I will discuss how the cell regulates its chromatin dynamics in response to the metabolism indicators AMPK (AMP-activated protein kinase). I will also show how chromatin motion and structure behave without the presence of key proteins such as RAD51 that aid in DNA damage. Finally I will go over future directions and improvements we can do to our current techniques to improve our understanding of chromatin’s role is various biological functions. We expect that the exploration of the spatiotemporal dynamics in live cells will facilitate the diagnosis, treatment, and prevention of cancers.
Advancing super-resolution microscopy for quantitative in-vivo imaging of chromatin nanodomains
(2024-12) Seitz, Clayton; Liu, Jing; Vemuri, Gautam; Cheng, Ruihua; Wassall, Stephen; Petrache, Horia
Single molecule localization microscopy (SMLM) techniques, such as direct stochastic optical reconstruction microscopy (dSTORM), can be used to produce a pointillist representation of fluorescently-labeled biological structures at diffraction-unlimited precision. This class of techniques permits localization of fluorescent molecules in the cell with nanometer precision and thus is commonly referred to as nanoscopy. Conventional nanoscopy utilizes the deactivation of standard fluorescent tags, followed by spontaneous or photoinduced reactivation, to resolve fluorophores at distances below the diffraction limit. While powerful, this approach has limited throughput and requires localization in sparse scenes. This dissertation introduces fluorescence nanoscopy and covers its innovation and application as discussed in the following papers: Quantum enhanced localization microscopy with a single photon avalanche diode array [ 1 ] leverages recent advancements in single photon avalanche diode array technology to count fluorescent emitters using a widefield microscope. Uncertainty-aware localization microscopy by variational diffusion [ 2 ] describes a novel algorithm that applies a diffusion model in order to model a posterior distribution on high resolution localization microscopy images, given low resolution inputs. role of the BRD4 phosphoswitch in the maintenance of chromatin nanodomains via super resolution microscopy and molecular dynamics simulation. We demonstrate that BRD4 phosphorylation regulates chromatin packing and mobility in mammalian nuclei.
A Computational Framework for Investigating mRNA Localization Patterns in Pancreatic Beta-Cells During Type 1 Diabetes Progression
(2024-12) Chang, Hok Wai; Petrache, Horia; Liu, Jing; Wassall, Stephen; Vemuri, Gautam; Syed, Farooq
Spatial transcriptomics improves transcriptomic studies by incorporating RNA localization information, which provides a more profound insight into cellular functions, interactions between cells, and their reactions to external stimuli. Single-molecule fluorescent in situ hybridization (smFISH) is a commonly utilized technique in spatial transcriptomics that allows for the accurate visualization of mRNA distribution in cells. This method aids in the quantitative evaluation of mRNA localization patterns by utilizing various physical properties, thereby illuminating processes such as transcription, nuclear export, and localized translation. Nevertheless, existing computational approaches for analyzing smFISH images often have constraints, concentrating primarily on cellular expression or specific biological contexts while overlooking broader physical analysis. In my PhD research, I created STProfiler, a comprehensive tool aimed at an unbiased physical examination of mRNA distribution. STProfiler includes an image analysis workflow that processes raw biological images to effectively detect mRNA and nuclei. It also employs machine learning techniques to biologically interpret mRNA spatial characteristics and categorize cells based on these features. My dissertation illustrates the use of STProfiler in multiple studies investigating the transcriptomic profiles of β-cells during the progression of type 1 diabetes (T1D), uncovering spatial transcriptomic diversity in β-cells. These investigations involve analyzing mRNA clusters and stress granules in pancreatic β-cells, measuring the physical characteristics of mRNAs linked to cellular stress and inflammation in mice developing T1D, evaluating the rise in HLA-DMB mRNA spliced variant in T1D, and exploring miRNA as a potential biomarker for T1D. Furthermore, STProfiler has also proven beneficial in tissue-wide spatial transcriptomics by creating masks for nuclei and cells from biological images and assigning mRNA transcripts to develop subcellular expression profiles. This capability allows for more thorough bioinformatic evaluations. In summary, STProfiler serves as a robust tool for both cell- and tissue-level spatial transcriptomics, offering an unbiased platform for researchers to investigate complex transcriptomic variations within cells.
Novel Materials for Spintronic Devices
(2024-12) Dale, Ashley; Cheng, Ruihua; Petrache, Horia I.; Gavrin, Andrew D.; Amin, Vivek Pravin; Dowben, Peter A.
Spintronic devices are devices which use the spin properties of atoms to store information. Such devices are predicted to be lower power. In this work, two Fe- II spin crossover molecules are analyzed as candidate novel materials for spintronic devices through computational and experimental work. The molecular activation energy for spin crossover molecule [Fe{H2B(pz)2}2(bipy)] in thin film on a ferroelectric substrate is estimated using Monte Carlo simulations of an Ising-like Model to be 88 meV when the substrate is polarized towards the thin film surface and 198 meV when the substrate is polarized away from the thin film surface. Additional Monte Carlo simulations suggests that beyond-nearest neighbor interactions are required for observed spin-state domain formation. The magnetic anisotropy and spectroscopic g factor for [Fe{H2B(pz) 2}2 (bipy)] molecules are characterized using X-ray magnetic circular dichroism measurements; thin films were dominated by magnetocrystalline anisotropy and the spin-orbit coupling energy was found to be 1.47 kJ m-3. Spin and orbital moment anisotropy estimations from the XMCD measurement were 30.9 and 5.04 meV molecule-1, respectively, and the zero-field g factor was estimated to be gz = 2.26. The optical energy gap for [Fe{HB(tz)3}2] is estimated to be 1.93±0.15 eV using UV-Vis spectroscopic measurements and a newly derived Tauc method for large molecules in solvent. Finally, the [Fe{HB(tz)3}2] molecule in thin film form is confirmed to have increased resistance in the high-spin state, with an on-off ratio of 103. These measurements contribute to the development of novel spintronic devices.
Study of the Valence Tautomer Complex [Co(sq)(cat)(3-tpp)2] for Applications in Molecular Spintronics
(2023-12) Phillips, Jared; Cheng, Ruihua; Gavrin, Andrew; Joglekar, Yogesh; Anasori, Babak; Kenning, Gregory
Molecular materials exhibiting bistability between two states are intriguing candidates for next generation electronic devices. Two similar classes of materials, known as spin crossover (SCO) and valence tautomers (VT) respectively, are of particular interest due to their multifunctional properties, which are controllable via several external parameters, such as temperature, light irradiation, pressure, magnetic field, and electric field. In recent years, considerable research has been dedicated to better understanding the underlying principles that govern the behavior of these materials, so that their implementation into nano-based devices might be achieved. In this report, a systematic study of the valence tautomer molecule [Co(sq)(cat)(3-tpp)2] is presented. In the first chapter, the phenomenon of valence tautomerism (VT) occurring in coordination compounds is introduced and described from the perspective of Crystal Field Theory (CFT). Further, the molecular structure and physical properties of the [Co(sq)(cat)(3-tpp)2] molecule are explored. The properties of the ferroelectric material Polyvinylidene fluoride- hexafluoropropylene (PVDF-HFP), and the 2-D Mxene Ti3C2 are also discussed. The next section details equipment development and experimental methods. Thin films of VT molecules were prepared from solution via a drop-casting approach. For thin film analysis, we have developed a custom made, fully automated Vibrating Sample Magnetometer (VSM) with a sensitivity on the order of 1 × 10-5 emu, as well as a fully automated, variable temperature, under vacuum electron transport stage, and a magneto-optic Kerr effect apparatus (MOKE). Additional experimental methods used to characterize the VT thin films include X-ray Absorption Spectroscopy (XAS), UV-visible Spectrometry (UV-Vis) and Differential Scanning Calorimetry. Experimental results obtained from these techniques are discussed and analyzed in the third section. PVDF-HFP polarization dependent isothermal spin state switching of [Co(sq)(cat)(3-tpp)2] is also discussed as well as the effects of doping [Co(sq)(cat)(3-tpp)2] with Ti3C2, followed by a conclusion and an outline of future work.
Short Range Probes to Extensions of the Standard Model
(2023-08) Bsaibes, Thomas; Decca, Ricardo; Petrache, Horia; Cheng, Ruihua; Joglekar, Yogesh; Gavrin, Andrew; Michael, Snow
As successful as the Standard Model has been in describing particle interactions, there are still many open questions it does not answer; the strong CP violation and the existence of dark matter among them. To address these issues many extensions to the Standard Model have been devised. Some of these extensions propose a new force mediating particle; a massive particle results in a potential described by a Yukawa-like interaction, while a massless exchange particle leads to power law type potentials. Limits on the strength of these interactions at the sub-micron range of separation between two particles are poorly characterized, but previous experiments conducted at IUPUI placed the best limits to date on the strength of a Yukawa-like interaction. Those experiments used a spherical test mass and a planar source mass. However, if a cylindrical test mass was used, the increased interaction volume of the cylinder would result in an increased sensitivity of about an order of magnitude over the spherical test mass experiment. Building such a system presents many challenges, namely the alignment of the cylinder with respect to the planar source mass. A capacitance based scheme to determine the alignment of a cylinder with respect to a plane will be discussed. The thesis concludes with an outline for a new type of measurement system. The new experiment attempts to induce a gravitational Π-pulse in a nanoshphere to probe extensions to the Standard Model.
Exceptional Points and their Consequences in Open, Minimal Quantum Systems
(2022-08) Muldoon, Jacob E.; Joglekar, Yogesh; Decca, Ricardo; Cheng, Rui; Vemuri, Gautam; Cincio, Lukasz
Open quantum systems have become a rapidly developing sector for research. Such systems present novel physical phenomena, such as topological chirality, enhanced sensitivity, and unidirectional invisibility resulting from both their non-equilibrium dynamics and the presence of exceptional points. We begin by introducing the core features of open systems governed by non-Hermitian Hamiltonians, providing the PT -dimer as an illustrative example. Proceeding, we introduce the Lindblad master equation which provides a working description of decoherence in quantum systems, and investigate its properties through the Decohering Dimer and periodic potentials. We then detail our preferred experimental apparatus governed by the Lindbladian. Finally, we introduce the Liouvillian, its relation to non-Hermitian Hamiltonians and Lindbladians, and through it investigate multiple properties of open quantum systems.
Beyond the Exceptional Point: Exploring the Features of Non-Hermitian PT Symmetric Systems
(2022-08) Agarwal, Kaustubh Shrikant; Joglekar, Yogesh N.; Vemuri, Gautam; Ou, Zhe “Jeff”; Petrache, Horia I.; Lukens, Joseph M.
Over the past two decades, open systems that are described by a non-Hermitian Hamiltonian have become a subject of intense research. These systems encompass classical wave systems with balanced gain and loss, semi-classical models with mode selective losses, and lossy quantum systems. The rapidly growing research on these systems has mainly focused on the wide range of novel functionalities they demonstrate. In this thesis, I intend to present some intriguing properties of a class of open systems which possess parity (P) and time-reversal (T) symmetry with a theoretical background, accompanied by the experimental platform these are realized on. These systems show distinct regions of broken and unbroken symmetries separated by a special phase boundary in the parameter space. This separating boundary is called the PT-breaking threshold or the PT transition threshold. We investigate non-Hermitian systems in two settings: tight binding lattice models, and electrical circuits, with the help of theoretical and numerical techniques. With lattice models, we explore the PT-symmetry breaking threshold in discrete realizations of systems with balanced gain and loss which is determined by the effective coupling between the gain and loss sites. In one-dimensional chains, this threshold is maximum when the two sites are closest to each other or the farthest. We investigate the fate of this threshold in the presence of parallel, strongly coupled, Hermitian (neutral) chains, and find that it is increased by a factor proportional to the number of neutral chains. These results provide a surprising way to engineer the PT threshold in experimentally accessible samples. In another example, we investigate the PT-threshold for a one-dimensional, finite Kitaev chain—a prototype for a p-wave superconductor— in the presence of a single pair of gain and loss potentials as a function of the superconducting order parameter, onsite potential, and the distance between the gain and loss sites. In addition to a robust, non-local threshold, we find a rich phase diagram for the threshold that can be qualitatively understood in terms of the band-structure of the Hermitian Kitaev model. Finally, with electrical circuits, we propose a protocol to study the properties of a PT-symmetric system in a single LC oscillator circuit which is contrary to the notion that these systems require a pair of spatially separated balanced gain and loss elements. With a dynamically tunable LC oscillator with synthetically constructed circuit elements, we demonstrate static and Floquet PT breaking transitions by tracking the energy of the circuit. Distinct from traditional mechanisms to implement gain and loss, our protocol enables parity-time symmetry in a minimal classical system.
Investigation of PT Symmetry Breaking and Exceptional Points in Delay-coupled Semiconductor Lasers
(2021-08) Wilkey, Andrew; Vemuri, Gautam; Joglekar, Yogesh; Liu, Jing; Ou, Jeff; Petrache, Horia
This research investigates characteristics of PT (parity-time) symmetry breaking in a system of two optically-coupled, time-delayed semiconductor lasers. A theoretical rate equation model for the lasers' electric fields is presented and then reduced to a 2x2 Hamiltonian model, which, in the absence of time-delay, is PT-symmetric. The important parameters we control are the temporal separation of the lasers, the frequency detuning, and the coupling strength. The detuning is experimentally controlled by varying the lasers' temperatures, and intensity vs. detuning behavior are examined, specifically how the PT-transition and the period and amplitude of sideband intensity oscillations change with coupling and delay. Experiments are compared to analytic predictions and numerical results, and all are found to be in good agreement. Eigenvalues, eigenvectors, and exceptional points of the reduced Hamiltonian model are numerically and analytically investigated, specifically how nonzero delay affects existing exceptional points.
Injection Current Modulated Parity-Time Symmetry in Coupled Semiconductor Lasers
(2021-08) Thomas, Luke; Vemuri, Gautam; Gavrin, Andrew; Petrache, Horia; Wassall, Stephen
This research investigates the characteristics of Parity Time symmetry breaking in two optically coupled, time delayed semiconductor lasers. A theoretical model is used to describe the controllable parameters in the experiment and intensity output of the coupled lasers. The PT parameters we control are the spatial separation between the two lasers, the frequency detuning, and the coupling strength. We find that the experimental data agrees with the predictions from the theoretical model confirming the intensity behaviors of the lasers, and the monotonic change in PT-threshold as a function of coupling scaled by the time delay.

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