Research Project 1: Binding Inhibitory Activity of PFD1140w antibodies against clinical isolates
- Binding Inhibitory Activity of PFD1140w antibodies against clinical isolates
- Supervisor(s):Dr Henrietta Mensah-Brown, Prof Gordon Awandare
- Contact details: hemensah-brown@ug.edu.gh
Summary of hosting Lab
| TThe Mensah-Brown lab at WACCBIP, University of Ghana works on malaria parasite biology and immunology, focused on parasite invasion strategies as wel as the identification and validation of potential targets for drug and vaccine development. This is particularly important since malaria remains a major global health challenge. The recent resurgence in malaria morbidity and mortality signals the need to identify and develop drugs and vaccines that can aid the elimination of malaria.. |
Project Description
| PFD1140w is a gene which has been shown to upregulated with var2CSA in placental malaria parasites. In our recent studies, we found that PFD1140w transcripts were similarly upregulated with var2CSA in parasites from children with severe malaria compared to parasites from children with uncomplicated malaria. Our unpublished data further showed that anti- PFD1140w antibody levels in children with severe were significantly elevated when compared to children with uncomplicated malaria, while anti-PFD1140w antibodies used in combination with anti-var2CSA antibodies showed the ability to disrupt parasite binding to CSA in a limited number of laboratory parasites. In this project, we will expand our studies to clinical isolates and more laboratory lines to confirm the binding inhibitory activity of these parasites |
Publications
| Francis SE, Malkov VA, Oleinikov AV, Rossnagle E, Wendler JP, Mutabingwa TK, Fried M, Duffy PE. Six genes are preferentially transcribed by the circulating and sequestered forms of Plasmodium falciparum parasites that infect pregnant women. Infect Immun. 2007 Oct;75(10):4838-50. doi: 10.1128/IAI.00635-07. Epub 2007 Aug 13. PMID: 17698567; PMCID: PMC2044550. Kumar V, Kaur J, Singh AP, Singh V, Bisht A, Panda JJ, Mishra PC, Hora R. PHISTc protein family members localize to different subcellular organelles and bind Plasmodium falciparum major virulence factor PfEMP-1. FEBS J. 2018 Jan;285(2):294- 312. doi: 10.1111/febs.14340. Epub 2017 Dec 10. PMID: 29155505. Fried M, Duffy PE. Analysis of CSA-binding parasites and antiadhesion antibodies. Methods Mol Med. 2002;72:555-60. doi: 10.1385/1-59259-271-6:555. PMID: 12125153. |
Major Lab techniques
| Sample processing, parasite culture, ELISA, Drug assays, Flow cytometry |
Research Project 2: Leveraging Calcium Ion and Biosynthesised Nanoparticles to Increase Antibiotic Effectiveness and Intercept AMR Pathways
- Thematic field of study: Leveraging Calcium Ion and Biosynthesised Nanoparticles to Increase Antibiotic Effectiveness and Intercept AMR Pathways
- Supervisor(s):Abiola Isawumi
- Contact details: isawumiabiola@gmail.com
Summary of hosting Lab
| Our group is investigating the antimicrobial resistance (AMR) mechanisms of novel superbugs (ESKAPE pathogens) and newly emerging Pan-African multidrug-resistant (MDR) pathogens prevalent and diversely distributed in hospital environments, especially those that are implicated in nosocomial infections in the Intensive Care Unit. We are advancing research efforts in hetero-resistance mechanisms, bacterial virulence and pathogenesis, lipopolysaccharide modifications, biofilm-motility interplay in bacterial resistance, toxin- antitoxin, and secretory systems. As we leverage phenotypic algorithms and molecular tools for developing diverse assays to potentiate antibiotic effectiveness and understand opportunistic pathogen antibiotic-evasion pathways, we are also taking advantage of nanoparticles for antibiotic delivery and phage technology to intercept AMR pathways to inform treatment strategies. |
Project Description
| Our previous study showed that calcium ions have the tendency to potentiate carbapenems against MDR Enterobacter cloacae. Conditional growth stress with calcium ions showed a 50% reduction in levels of carbapenem resistance. With this preliminary information, we posit that calcium ions in conjugation with biosynthesised nanoparticles can outcompete lipopolysaccharides localised on the Gram-negative bacterial membrane surface to facilitate antibiotic permeability. This, in turn, can influence the interception of AMR pathways and provide a relevant therapeutic insights to inform treatment strategies. |
Publications
| Isawumi A, Abban MK, Ayerakwa EA, Mosi L. Calcium Potentiated Carbapenem Effectiveness Against Resistant Enterobacter Species. Microbiology Insights. 2022;15. doi:10.1177/11786361221133728 Isawumi A, Ayerakwa EA, Abban MK, Mosi L. Expression profiles of sporulation genes in multidrug-resistant Bacillus species isolated from intensive care units of Ghanaian hospital. Experimental Biology and Medicine. 2023;248(6):501-507. doi:10.1177/15353702231160336 Molly Kukua Abban, Eunice Ampadubea Ayerakwa, Lydia Mosi, Abiola Isawumi. The burden of hospital acquired infections and antimicrobial resistance, Heliyon, 2023, e20561, ISSN 2405- 8440, https://doi.org/10.1016/j.heliyon.2023.e20561 Abban RL, Kwabena S, Duodu S, Mosi L, Abiola Isawumi (2023) Targeting Proteus mirabilis BAM Complex Proteins for Development of Novel Antibiotics. Research Ideas and Outcomes 9: e106849. https://doi.org/10.3897/rio.9.e106849 A. Isawumi, A. Kukua Abban, A. Duodu, A. Mosi, M. Valvano (2020). Klebsiella oxytoca: Evolving superbug from Ghanaian Hospitals. International Journal of Infectious Diseases, 101(1):43-44. https://doi.org/10.1016/j.ijid.2020.09.147. |
Major Lab techniques
| Sample processing, Bacterial culturing and characterization, cell culturing, drug-assays development, microscopy, nanoparticle sysnthesis set up, gene expression analysis, molecular biology assays, LPS profiling, phage isolation, collaborative research, documentation and reporting, mentoring, data curation and analysis |
Research Project 3: Evolutionary changes in mycolactone producing mycobacteria; the role of insertion sequence
- Thematic field of study: Evolutionary changes in mycolactone producing mycobacteria; the role of insertion sequence
- Supervisor(s):Prof. Lydia Mosi
- Contact details: lmosi@ug.edu.gh
Summary of hosting Lab
| The Mosi lab focuses on unearthing transmission of the neglected tropical skin disease, Buruli ulcer, developing early diagnostic tools and identifying antimicrobial resistance in secondary bacteria with the lesions. The lab also does research on the integration of diagnosis and management of neglected tropical diseases. Her lab is a core member of the World Health Organization Laboratory Network for Skin NTDs ( SkinNTD-LABNET). |
Project Description
| Based on the evolution of endosymbiont bacteria, the African MU strains are in stage two of evolutionary adaptation after pMUM plasmid acquisition. This was characterized by increased pseudogene numbers, further genome erosion, the loss of insertion sequences, increased purifying selection (decreasing non-synonymous mutation), and the decrease in pseudogenes in both African lineages. The loss of insertion sequences (IS2404) in the second stage has implications for the diagnosis of BU because of its use in diagnosis. This requires further studies into the variations in the number of IS2404 and other insertion sequences in the genome, and how their elimination can impact diagnosis to inform better diagnostic strategies. |
Publications
| Kyei-Baffour ES, Owusu-Boateng K, Isawumi A, Mosi L. Pseudogenomic insights into the evolution of Mycobacterium ulcerans. BMC Genomics. 2024 Jan 22;25(1):87. doi: 10.1186/s12864-024-10001-1. PMID: 38253991; PMCID: PMC10802024. Gyamfi E, Dogbe MA, Quaye C, Affouda AA, Kyei-Baffour E, Awuku-Asante D, Sarpong-Duah M, Mosi L. Variable Number Tandem Repeat Profiling of Mycobacterium ulcerans Reveals New Genotypes in Buruli Ulcer Endemic Communities in Ghana and Côte d’Ivoire. Front Microbiol. 2022 Jun 23;13:872579. doi: 10.3389/fmicb.2022.872579. PMID: 35814673; PMCID: PMC9262091. Addo SO, Mensah GI, Mosi L, Abrahams AOD, Addo KK. Genetic diversity and drug resistance profiles of Mycobacterium tuberculosis complex isolates from patients with extrapulmonary tuberculosis in Ghana and their associated host immune responses. IJID Reg. 2022 Jun 27;4:75- 84. doi: 10.1016/j.ijregi.2022.06.005. PMID: 35813561; PMCID: PMC9263986. Dassi C, Mosi L, Narh CA, Quaye C, Konan DO, Djaman JA, Bonfoh B. Distribution and Risk of Mycolactone-Producing Mycobacteria Transmission within Buruli Ulcer Endemic Communities in Côte d’Ivoire. Trop Med Infect Dis. 2017 Feb 26;2(1):3. doi: 10.3390/tropicalmed2010003. PMID: 30270862; PMCID: PMC6082052. Narh CA, Mosi L, Quaye C, Dassi C, Konan DO, Tay SC, de Souza DK, Boakye DA, Bonfoh B. Source tracking Mycobacterium ulcerans infections in the Ashanti region, Ghana. PLoS Negl Trop Dis. 2015 Jan 22;9(1):e0003437. doi: 10.1371/journal.pntd.0003437. PMID: 25612300; PMCID: PMC4303273. |
Major Lab techniques
| Molecular biology assays, Sequencing and Bioinformatics. |
Research Project 4: Antitrypanosomal activity and mode of action of compounds isolated from Ghanaian plant extracts
- Thematic field of study: Antitrypanosomal activity and mode of action of compounds isolated from Ghanaian plant extracts
- Supervisor(s):Dr Theresa Manful Gwira
- Contact details: tmgwira@ug.edu.gh
Summary of hosting Lab
| The Gwira research group the West African Centre for Cell Biology of Infectious Pathogens (WACCBIP), University of Ghana is interested in research in two main areas (I) Biology and genotyping of trypanosomes in animals and tsetse flies, and (II) Management of animal African trypanosomiasis and leishmaniasis. The current research on Animal African Trypanosomiasis (AAT) includes the characterization of lifetime infection with trypanosomes in cattle and tsetse flies, tissue tropism, understanding drug resistance to the common antitrypanosomals used for the treatment of AAT and drug discovery for AAT by exploring both natural products and synthetic compounds. Our work on leishmaniasis is focused on drug discovery, host-pathogen interaction and iron homeaostasis in leishmania infections. |
Project Description
| The urgent need for a more efficient chemotherapy for trypanosomiasis and leishmaniasis can be provided by evaluating possible target metabolic pathways for the action of antitrypanosomals and antileishmanials, alongside efficient and systematic screening (aided by spectroscopy, spectrometry, high-throughput RNA sequencing (RNASeq), microscopy and bioassays) of both plants and microbial natural products for novel leads. This project will involve screening of product that are routinely used in traditional remedies for the treatment and management of protozoan diseases in Ghana (West Africa) to characterize the active principles behind the efficacy of these remedies in trypanosomes. Some of the activities for the projects includes parasite culture and maintenance, drug-activity assays, microscopy. |
Publications
| Manful, E-E., Dofuor, A. K. and Gwira, T. M. (2024). The role of tryptophan derivatives as anti-kinetoplastid agents. Heliyon 10 (1) Twumasi, E. B., Akazue, P. I., Kyeremeh, K., Gwira, T. M., Keiser, J., Cho-Ngwa, F., Flint, A., Anibea, B., Bonsu, E. Y., Amewu, A. K., Amoah, L. E., Regina Appiah-Opong, R. and Osei-Safo, D. (2020). Antischistosomal, antionchocercal and antitrypanosomal potentials of some Ghanaian traditional medicines and their constituents. PLoS Negl Trop Dis. 14(12); e0008919 Dofuor, A. K., Ayertey, F., Bolah, P., Djameh, G. I., Kyeremeh, K., Ohashi, M., Laud Kenneth Okine, L. K. and Gwira, T. M. (2020). Isolation and Antitrypanosomal Characterization of Furoquinoline and Oxylipin from Zanthoxylum zanthoxyloides. Biomolecules, 10(12), 1670 Amisigo, C. M., Antwi, C. A, Adjimani, J. P. and Gwira, T. M. (2019). In vitro anti- trypanosomal effects of selected phenolic acids on Trypanosoma brucei. PLoS ONE 14(5): e0216078. https://doi.org/10.1371/journal.pone.0216078 Antwi, C. A, Amisigo, C. M., Adjimani, J. P. and Gwira, T. M. (2019). In vitro activity and mode of action of phenolic compounds on Leishmania donovani. PLoS Negl Trop Dis, 13(2), pp e0007206. |
Major Lab techniques
| SParasite culture and maintenance, drug-activity assays, microscopy, documentation and reporting, Data analysis and oral presentation |
Research PhD Project: Phenolic compounds and their modulation of iron homeostasis in Leishmania
- Thematic field of study: Phenolic compounds and their modulation of iron homeostasis in Leishmania
- Supervisor(s):Dr Theresa Manful Gwira
- Contact details: tmgwira@ug.edu.gh
Summary of hosting Lab
| The Gwira research group at the West African Centre for Cell Biology of Infectious Pathogens (WACCBIP), University of Ghana is interested in research in two main areas (I) Biology and genotyping of trypanosomes in animals and tsetse flies, and (II) Management of animal African trypanosomiasis and leishmaniasis. The current research on Animal African Trypanosomiasis (AAT) includes the characterization of lifetime infection with trypanosomes in cattle and tsetse flies, tissue tropism, understanding drug resistance to the common antitrypanosomals used for the treatment of AAT and drug discovery for AAT by exploring both natural products and synthetic compounds. Our work on leishmaniasis is focused on drug discovery, host-pathogen interaction and iron homeaostasis in leishmania infections. |
Project Description
| Iron is an essential element that is needed by all living organisms including trypanosomes and Leishmania. Although iron plays a central role in many pathways in these organisms, little is known about the regulation as well as proteins involved in cellular uptake. In humans iron is regulated by iron regulatory proteins (IRP), which bind to iron-responsive elements (IRE), to control the expression levels of essential elements of the iron acquisition pathway. However, the processes are not well understood in Leishmania. The work is to characterise the factors involved in iron homeostasis. To address the aim, this work will involve a combination of in vitro and in vivo assays, and the long-term goal is a better understanding of iron metabolism which may lead to the discovery of new drug targets. |
Publications
| Manful, E-E., Dofuor, A. K. and Gwira, T. M. (2024). The role of tryptophan derivatives as anti- kinetoplastid agents. Heliyon 10 (1) Sakyi, P.O., Kwofie, S. K., Tuekpe, J. K., Gwira, T. M., Broni, E. WA Miller III, W. A. and Amewu, R. K. (2023). Inhibiting Leishmania donovani Sterol Methyltransferase to Identify Lead Compounds Using Molecular Modelling. Pharmaceuticals 16 (3), 330 Twumasi, E. B., Akazue, P. I., Kyeremeh, K., Gwira, T. M., Keiser, J., Cho-Ngwa, F., Flint, A., Anibea, B., Bonsu, E. Y., Amewu, A. K., Amoah, L. E., Regina Appiah-Opong, R. and Osei-Safo, D. (2020). Antischistosomal, antionchocercal and antitrypanosomal potentials of some Ghanaian traditional medicines and their constituents. PLoS Negl Trop Dis. 14(12); e0008919 Amisigo, C. M., Antwi, C. A, Adjimani, J. P. and Gwira, T. M. (2019). In vitro anti-trypanosomal effects of selected phenolic acids on Trypanosoma brucei. PLoS ONE 14(5): e0216078. https://doi.org/10.1371/journal.pone.0216078 Antwi, C. A, Amisigo, C. M., Adjimani, J. P. and Gwira, T. M. (2019). In vitro activity and mode of action of phenolic compounds on Leishmania donovani. PLoS Negl Trop Dis, 13(2), ppe 0007206. |
Major Lab techniques
| SParasite culture and maintenance, drug-activity assays, microscopy, RT-PCR, documentation and reporting, Data analysis and oral presentation |
Links to the programmes in the University
WACCBIP PhD programmes
https://www.waccbip.org/our-programmes/doctoral/
WACCBIP Masters programmes
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