
Dr Dany Beste
Academic and research departments
School of Biosciences and Medicine, Faculty of Health and Medical Sciences.Biography
My first degree was in Biochemistry (University of Sussex) after which I had a very successful career as a Biomedical Scientist within the NHS (Public Health Laboratory Services, Streptococcus and Diphtheria Reference Laboratory, Hospital of Tropical Diseases), industry (GR Micro Ltd) and VSO (Malawi College of Health Sciences). The experiences of working as a Microbiology Lecturer in Malawi (VSO) inspired me to go back to University (MSc in Medical Microbiology, London School of Hygiene and Tropical Medicine; PhD project Analysis of a Chemostat Model of TB persistence using a Global Systems Approach, EU funded at the University of Surrey). After two exciting interdisciplinary projects (Wellcome and BBSRC funded) on the systems biology of tuberculosis I was appointed as a Lecturer in Microbial Metabolomics. I am now best known for my expertise in exploring the metabolic phenotype of Mycobacterium tuberculosis in different conditions (back to biochemistry).
University roles and responsibilities
- Programme Leader for MSc Medical Microbiology
Affiliations and memberships
Research
Research interests
My interest in tuberculosis ignited whilst working as a Biomedical Scientist in Malawi (1995-1997) when 25% of Malawians (often co-infected with HIV) were dying from this disease and this experience led me to a PhD studying the physiology of Mycobacterium tuberculosis.
Tuberculosis is the top infectious killer, the main cause of death related to antitbiotc resistance and the leading cause of death in HIV patients. Whilst we have reduced global death rates from tuberculosis increasing antimicrobial resistance threatens to destabilise control measures.
The road-map to controlling tuberculosis must include fundamental tuberculosis research in order to understand the basic biology of M. tuberculosis and its interaction with the human host.
Using an integrated approach of genetics, metabolomics, biochemical assays, transcriptomics, chemostat cultures and intracellular studies my group is focused on answering fundamental questions in TB physiology which still remain unanswered for M. tuberculosis such as: Which nutrients does M. tuberculosis utilise in the host?; What metabolic pathways are required for intracellular growth?; How does M. tuberculosis adapt to slow growth rate and different nutrients? How does metabolism impact on the development of antimicrobial resistance?
Our ultimate goal is to translate our findings into new chemotherapeutic strategies against tuberculosis.
Indicators of esteem
Editorial Board of Microbiology
Supervision
Postgraduate research supervision
My teaching
Using interactive teaching methods and integrating primary literature into the classroom I strive to expose students to the exciting world of science and encourage active participation in scientific discovery related to their future occupation.
Undergraduate
I teach on the following courses:
- Biochemistry BSc (Hons)
- Biological Sciences BSc (Hons)
- Food Science and Nutrition BSc (Hons)
- Microbiology BSc (Hons)
- Nutrition BSc (Hons)
- Nutrition and Dietetics BSc (Hons)
- Veterinary Biosciences BSc (Hons).
I teach the following modules:
- BMS1026: Introduction to the Microbial World
- BMS2044: Microbial Communities
- BMS3079: Human Microbial Diseases.
Postgraduate
I teach on the MSc Medical Microbiology course.
I teach the following modules:
- MMIM013/MMIM030: Research Project
- MMIM016: Management of Scientific Research
- MMIM024: Pathogenesis of Infectious Diseases
- MMIM029: Journal Club.
My publications
Highlights
Borah, Khushboo, Mendum, Tom A., Hawkins, Nathaniel, Ward, Jane, Beale, Michael, Larrouy-Maumus, Gerald, Bhatt, Apoorva, Pichler, Harald, Moulin, Martine, Haertlein, Michael, Forsyth, Trevor, Noack, Stephan, Goulding, Celia McFadden, Johnjoe, Beste, Dany J. V. Metabolic flux partitioning between the TCA cycle and glyoxylate shunt combined with a reversible methyl citrate cycle provide nutritional flexibility for Mycobacterium tuberculosis. bioRxiv 2021.01.29.428863; doi: https://doi.org/10.1101/2021.01.29.428863
Burley K. H., Cuthbert B. J., Basu P., Newcombe J. , Irimpan E. M. , Quechol R. , Foik I. P. , Mobley D. L. , Beste D. J. V. , Goulding C. W. Structural and Molecular Dynamics of Mycobacterium tuberculosis Malic Enzyme, a Potential Anti-TB Drug Target. ACS Infect Dis. 2021 Jan 8;7(1):174-188. doi: 10.1021/acsinfecdis.0c00735. Epub 2020 Dec 23. PMID: 33356117.
Mackenzie, Jared S., Lamprecht, Dirk A., Asmal, Rukaya, Adamson, John H. ,Borah, Khushboo, Beste, Dany J. V., Lee, Bei Shi, Pethe, Kevin, Rousseau, Simon, Krieger, Inna, Sacchettini, James C.,Glasgow, Joel N.,Steyn, Adrie J. C.Bedaquiline reprograms central metabolism to reveal glycolytic vulnerability in Mycobacterium tuberculosis. Nat Commun 11, 6092 (2020). https://doi.org/10.1038/s41467-020-19959-4.
Publications
The market for solvent production is predicted to reach $43.4 billion in 2018, with n-butanol having over 20% market share value where n-Butanol is the chemical precursor of several industrially important products, such as butyl-acetate, butyl-acrylate, glycol-ethers, and plasticisers. Butanol is currently produced from crude oil, and therefore in light of dwindling fossil fuel reserves, and more importantly, the need for green and clean production processes, synthesis of bio-butanol from biomass using Clostridia represents a viable and desirable alternative method.
This project focuses on the metabolic and physiologic characterisation of the acetone-butanol-ethanol (ABE) producing species Clostridium saccharoperbutylacetonicum (Csb). A minimal medium for Csb was defined based on literature data, modified by the addition of glutamate to support growth. Interestingly, batch cultures using this medium showed that Csb was able to grow and produce butanol under aerobic conditions, with titres of approximately 74% of those observed under anaerobic conditions. Steady state cultures in chemostats are essential to elucidate and characterise physiological features of microorganisms. Steady state cultures of Csb were used to determine the effect of acid production on solventogenesis, bacterial growth, and energy metabolism. Studies at different pH in the range 5.5 to 6.5 showed no correlation with the onset of solventogenesis. However, the pH and the growth rate seem to influence the productivity of butanol. In those experiments, significant increases in the production rate of butanol were observed when the dilution (growth) rate increased from 0.01 h-1 to 0.03 h-1 and the pH decreased from 6.5 to 5.5. Growth is potentially linked to production rate due to an increased demand for ATP and NADH recycling.
The use of genome scale metabolic models allows for the interpretation of metabolic and physiological changes upon changes in the culture conditions. A metabolic model of Csb was constructed based on the genome sequence of the microorganism and incorporating biomass synthesis equations specific for Csb which were constructed based on the analysis of the composition of the cells grown in the chemostat experiments, as opposed to current models that use biomass composition from related species (e.g. B. subtilis). The metabolic model was used to perform flux balance analysis to identify and interpret the changes in the distribution of metabolic fluxes that would explain the metabolic changes observed in Csb cultured under different conditions.
This work has demonstrated the basis for the presence of monophasic solventogenesis in C. saccharoperbutylacetonicum and provided important tools (defined media, GSMN equations) to improve industrial scale production of renewable sources of carbon-based feedstocks and thus reducing reliance on crude oil.
Additional publications
Borah, Khushboo, Mendum, Tom A., Hawkins, Nathaniel, Ward, Jane, Beale, Michael, Larrouy-Maumus, Gerald, Bhatt, Apoorva, Pichler, Harald, Moulin, Martine, Haertlein, Michael, Forsyth, Trevor, Noack, Stephan, Goulding, Celia McFadden, Johnjoe, Beste, Dany J. V. Metabolic flux partitioning between the TCA cycle and glyoxylate shunt combined with a reversible methyl citrate cycle provide nutritional flexibility for Mycobacterium tuberculosis. bioRxiv 2021.01.29.428863; doi: https://doi.org/10.1101/2021.01.29.428863
Burley K. H., Cuthbert B. J., Basu P., Newcombe J. , Irimpan E. M. , Quechol R. , Foik I. P. , Mobley D. L. , Beste D. J. V. , Goulding C. W. Structural and Molecular Dynamics of Mycobacterium tuberculosis Malic Enzyme, a Potential Anti-TB Drug Target. ACS Infect Dis. 2021 Jan 8;7(1):174-188. doi: 10.1021/acsinfecdis.0c00735. Epub 2020 Dec 23. PMID: 33356117.
Mackenzie, Jared S., Lamprecht, Dirk A., Asmal, Rukaya, Adamson, John H. ,Borah, Khushboo, Beste, Dany J. V., Lee, Bei Shi, Pethe, Kevin, Rousseau, Simon, Krieger, Inna, Sacchettini, James C.,Glasgow, Joel N.,Steyn, Adrie J. C. Bedaquiline reprograms central metabolism to reveal glycolytic vulnerability in Mycobacterium tuberculosis. Nat Commun 11, 6092 (2020). https://doi.org/10.1038/s41467-020-19959-4.