Dissertation/ Thesis
Mathematical modelling of cholesterol metabolism in Mycobacterium tuberculosis
| Title: | Mathematical modelling of cholesterol metabolism in Mycobacterium tuberculosis |
|---|---|
| Authors: | De la Harpe, Alana |
| Contributors: | Snoep, Jacky L., Warner, D., Stellenbosch University. Faculty of Science. Dept. of Biochemistry. |
| Publisher Information: | Stellenbosch University |
| Publication Year: | 2025 |
| Collection: | Stellenbosch University: SUNScholar Research Repository |
| Subject Terms: | Mycobacterium tuberculosis -- Pathogenesis, Tuberculosis -- Genetic aspects, Tuberculosis -- Immunological aspects, Cholesterol -- Metabolism -- Mathematical models, Genomes -- Data processing, Drug targeting, Mycobacterium tuberculosis -- Treatment |
| Description: | Thesis (PhD)--Stellenbosch University, 2025. ; de la Harpe, A. 2025. Mathematical modelling of cholesterol metabolism in Mycobacterium tuberculosis. Unpublished doctoral dissertation. Stellenbosch: Stellenbosch University [online]. Available: https://scholar.sun.ac.za/items/efcb2a03-dfaa-4497-a6f7-a7925423bd77 ; ENGLISH ABSTRACT: Tuberculosis (TB) remains a global health challenge with significant mortality due to Mycobacterium tuberculosis, a pathogen adept at evading host immune responses and persisting in nutrient-poor environments. Although curable, issues such as latent infection, treatment adherence, and the emergence of multidrug-resistant strains highlight the urgent need for novel therapeutic strategies. Approximately one-quarter of the global population is estimated to have latent TB infection (LTBI). A notable characteristic of M. tuberculosis is its ability to metabolise cholesterol, a key component of host membranes, via a specialised pathway crucial for its survival and persistence. Targeting this pathway presents a promising avenue for new drug development. Genome-scale models integrate computational and experimental data to simulate the entirety of an organism’s metabolic processes, providing insights into metabolic networks and vulnerabilities exploitable for therapeutic interventions. We developed and validated a new genome-scale metabolic model for Mycolicibacterium smegmatis, iADLH1356, consisting of 1356 genes, 1672 reactions, and 1245 metabolites. M. smegmatis is commonly used in laboratory settings for studying M. tuberculosis, as it possesses similar genetic and metabolic characteristics. Additionally, we updated and validated an existing genome-scale model for M. tuberculosis, iEK1011_2.1, with a focus on the cholesterol metabolic pathway to identify potential drug targets. The updated model consists of 1016 genes, 1259 reactions, and 1018 metabolites. Using these two models, we demonstrated various applications of genome-scale models, including analysing growth on cholesterol, ... |
| Document Type: | thesis |
| File Description: | xviii, 211 pages : illustrations; application/pdf |
| Language: | unknown |
| Relation: | https://scholar.sun.ac.za/handle/10019.1/132131 |
| Availability: | https://scholar.sun.ac.za/handle/10019.1/132131 |
| Rights: | Stellenbosch University |
| Accession Number: | edsbas.9B198344 |
| Database: | BASE |
| FullText | Text: Availability: 0 CustomLinks: – Url: https://scholar.sun.ac.za/handle/10019.1/132131# Name: EDS - BASE (ns324271) Category: fullText Text: View record from BASE |
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| Header | DbId: edsbas DbLabel: BASE An: edsbas.9B198344 RelevancyScore: 822 AccessLevel: 3 PubType: Dissertation/ Thesis PubTypeId: dissertation PreciseRelevancyScore: 821.935607910156 |
| IllustrationInfo | |
| Items | – Name: Title Label: Title Group: Ti Data: Mathematical modelling of cholesterol metabolism in Mycobacterium tuberculosis – Name: Author Label: Authors Group: Au Data: <searchLink fieldCode="AR" term="%22De+la+Harpe%2C+Alana%22">De la Harpe, Alana</searchLink> – Name: Author Label: Contributors Group: Au Data: Snoep, Jacky L.<br />Warner, D.<br />Stellenbosch University. Faculty of Science. Dept. of Biochemistry. – Name: Publisher Label: Publisher Information Group: PubInfo Data: Stellenbosch University – Name: DatePubCY Label: Publication Year Group: Date Data: 2025 – Name: Subset Label: Collection Group: HoldingsInfo Data: Stellenbosch University: SUNScholar Research Repository – Name: Subject Label: Subject Terms Group: Su Data: <searchLink fieldCode="DE" term="%22Mycobacterium+tuberculosis+--+Pathogenesis%22">Mycobacterium tuberculosis -- Pathogenesis</searchLink><br /><searchLink fieldCode="DE" term="%22Tuberculosis+--+Genetic+aspects%22">Tuberculosis -- Genetic aspects</searchLink><br /><searchLink fieldCode="DE" term="%22Tuberculosis+--+Immunological+aspects%22">Tuberculosis -- Immunological aspects</searchLink><br /><searchLink fieldCode="DE" term="%22Cholesterol+--+Metabolism+--+Mathematical+models%22">Cholesterol -- Metabolism -- Mathematical models</searchLink><br /><searchLink fieldCode="DE" term="%22Genomes+--+Data+processing%22">Genomes -- Data processing</searchLink><br /><searchLink fieldCode="DE" term="%22Drug+targeting%22">Drug targeting</searchLink><br /><searchLink fieldCode="DE" term="%22Mycobacterium+tuberculosis+--+Treatment%22">Mycobacterium tuberculosis -- Treatment</searchLink> – Name: Abstract Label: Description Group: Ab Data: Thesis (PhD)--Stellenbosch University, 2025. ; de la Harpe, A. 2025. Mathematical modelling of cholesterol metabolism in Mycobacterium tuberculosis. Unpublished doctoral dissertation. Stellenbosch: Stellenbosch University [online]. Available: https://scholar.sun.ac.za/items/efcb2a03-dfaa-4497-a6f7-a7925423bd77 ; ENGLISH ABSTRACT: Tuberculosis (TB) remains a global health challenge with significant mortality due to Mycobacterium tuberculosis, a pathogen adept at evading host immune responses and persisting in nutrient-poor environments. Although curable, issues such as latent infection, treatment adherence, and the emergence of multidrug-resistant strains highlight the urgent need for novel therapeutic strategies. Approximately one-quarter of the global population is estimated to have latent TB infection (LTBI). A notable characteristic of M. tuberculosis is its ability to metabolise cholesterol, a key component of host membranes, via a specialised pathway crucial for its survival and persistence. Targeting this pathway presents a promising avenue for new drug development. Genome-scale models integrate computational and experimental data to simulate the entirety of an organism’s metabolic processes, providing insights into metabolic networks and vulnerabilities exploitable for therapeutic interventions. We developed and validated a new genome-scale metabolic model for Mycolicibacterium smegmatis, iADLH1356, consisting of 1356 genes, 1672 reactions, and 1245 metabolites. M. smegmatis is commonly used in laboratory settings for studying M. tuberculosis, as it possesses similar genetic and metabolic characteristics. Additionally, we updated and validated an existing genome-scale model for M. tuberculosis, iEK1011_2.1, with a focus on the cholesterol metabolic pathway to identify potential drug targets. The updated model consists of 1016 genes, 1259 reactions, and 1018 metabolites. Using these two models, we demonstrated various applications of genome-scale models, including analysing growth on cholesterol, ... – Name: TypeDocument Label: Document Type Group: TypDoc Data: thesis – Name: Format Label: File Description Group: SrcInfo Data: xviii, 211 pages : illustrations; application/pdf – Name: Language Label: Language Group: Lang Data: unknown – Name: NoteTitleSource Label: Relation Group: SrcInfo Data: https://scholar.sun.ac.za/handle/10019.1/132131 – Name: URL Label: Availability Group: URL Data: https://scholar.sun.ac.za/handle/10019.1/132131 – Name: Copyright Label: Rights Group: Cpyrght Data: Stellenbosch University – Name: AN Label: Accession Number Group: ID Data: edsbas.9B198344 |
| PLink | https://search.ebscohost.com/login.aspx?direct=true&site=eds-live&db=edsbas&AN=edsbas.9B198344 |
| RecordInfo | BibRecord: BibEntity: Languages: – Text: unknown Subjects: – SubjectFull: Mycobacterium tuberculosis -- Pathogenesis Type: general – SubjectFull: Tuberculosis -- Genetic aspects Type: general – SubjectFull: Tuberculosis -- Immunological aspects Type: general – SubjectFull: Cholesterol -- Metabolism -- Mathematical models Type: general – SubjectFull: Genomes -- Data processing Type: general – SubjectFull: Drug targeting Type: general – SubjectFull: Mycobacterium tuberculosis -- Treatment Type: general Titles: – TitleFull: Mathematical modelling of cholesterol metabolism in Mycobacterium tuberculosis Type: main BibRelationships: HasContributorRelationships: – PersonEntity: Name: NameFull: De la Harpe, Alana – PersonEntity: Name: NameFull: Snoep, Jacky L. – PersonEntity: Name: NameFull: Warner, D. – PersonEntity: Name: NameFull: Stellenbosch University. Faculty of Science. Dept. of Biochemistry. IsPartOfRelationships: – BibEntity: Dates: – D: 01 M: 01 Type: published Y: 2025 Identifiers: – Type: issn-locals Value: edsbas |
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