Electronic Theses and Dissertations (Masters)

Permanent URI for this collection

https://hdl.handle.net/10539/38020

Browse

Browsing Electronic Theses and Dissertations (Masters) by SDG "SDG-4: Quality education"

Now showing 1 - 2 of 2
  • Thumbnail Image
    Item
    Chromatin accessibility changes during early monocyte-to-macrophage differentiation
    (University of the Witwatersrand, Johannesburg, 2024) Xu, Yi Fan; Meyer, V.; Gentle, N .
    The differentiation of monocytes into macrophages is a crucial process that enhances the local immune response against infection by recruiting monocytes to local tissues and transforming them into macrophages. The changes in gene expression associated with this process are known to be regulated by various mechanisms, including the chromatin accessibility landscape. Previous in vitro studies have shown that promonocytic THP-1 cells can differentiate into macrophage-like cells following treatment with phorbol 12-myristate 13-acetate (PMA). While previous studies have attempted to track the differentiation process over time, there has been a lack of research specifically focusing on earlier time points. Therefore, in this study, we used various publicly available RNA-seq, ATAC-seq and ChIP-seq datasets to describe the early events involved in monocyte-to-macrophage differentiation, using THP-1 cells treated with 100 ng/ml PMA for 24 hours as the model system. ATAC-seq data were aligned to the reference human genome (GRCh38) using Bowtie2 and chromatin accessibility peaks were identified using HMMRATAC. Differentially accessible chromatin regions (|L2FC| > 2; FDR < 0.05) were identified using DiffBind, and were annotated based on their cis-regulatory features. These included promoter regions (based on the GENCODE v40 annotations of the human genome) and THP-1-specific enhancers (defined as known enhancers within the GeneHancer database with an overlapping, THP-1-specific, H3K27ac mark). These cis-regulatory features were then associated with genes found to be significantly differentially expressed in response to PMA treatment (|L2FC| > 2; p.adj < 0.05), following quantification of gene expression using Salmon and differential gene expression analysis using DESeq2. The results of this study revealed that the early response to PMA in THP-1 cells is linked to changes in both gene expression and chromatin accessibility. These changes in both gene expression and chromatin accessibility were shown to be linked with inflammatory responses and cell migration activities. Although there was only a limited association between changes in gene expression and chromatin accessibility at the 24-hour time point, opening of chromatin at promoter and enhancer regions and increased gene expression was observed for many genes previously reported to be involved in the process of monocyte-to-macrophage differentiation, including CSF1, CSF1R, and IL-1α/β. This suggests that changes in chromatin accessibility at cis-regulatory elements taking place early in the differentiation process drive the changes in gene expression necessary for monocyte-to-macrophage differentiation
  • Thumbnail Image
    Item
    Skyrmions and vectorial wavefunctions
    (University of the Witwatersrand, Johannesburg, 2024) Ornelas, Pedro; Forbes , Andrew
    The study and generation of robust structured light stand as compelling areas of focus in the exploration of future classical and quantum photonic technologies. While the appeal of structuring light in all its degrees of freedom (DOFs) is undeniable, achieving the generation of intricate light resilient to noise from multiple sources, such as faulty detectors, stray white light, and atmospheric turbulence, is imperative for its practical integration into forthcoming technologies. Recently, there has been a lot of interest in generating states of light with identifiable topological features which are robust to local deformations thus providing such states with a possible mechanism for noise rejection. Topological structures known as optical skyrmions have garnered a lot of interest in the optics community of late as their magnetic counterparts have shown great promise as potential low-power information carriers. It has been shown that skyrmionic structures may be realised in classical free-space optical beams where their spatial and polarization DOFs are appropriately combined and manipulated to generate what are known as vector beams. Furthermore with the emergence of quantum structured light allowing for the manipulation of an individual photon’s DOFs, such topological structures may also be utilized as a resource for photonic based quantum technologies. In this dissertation we investigate the generation of classical optical skyrmions through the use of Bessel-Gaussian optical modes possessing interesting propagation dynamics which mimic magnetic systems under the application of a magnetic field. Furthermore, we extend the study of optical skyrmions to the quantum realm by generating and characterizing the topology of the quantum analogue to classical vector beams: hybrid entangled states where the spatial DOF of one photon is entangled with the polarization DOF of another. In this case the skyrmionic topology emerges as a shared property of both photons and can be identified through investigating their mutual correlations. We postulate a novel topological characterization of entangled states with the corollary that smooth deformations of these states do not change their topology and thus do not change how they are characterized. We show that the topology remains intact even when entanglement is fragile and further discuss how a typical mechanism for entanglement decay can be characterized as a smooth deformation. Lastly, we investigate the topological resilience of hybrid entangled states in the presence of isotropic noise usually attributed to external sources. We demonstrate the invariance of the topology of these states to varying levels of isotropic noise and discuss the associated mechanism for this invariance.