Cancer Metastasis: Insights from Cytoskeletal Dynamics, In Silico molecular modelling and drug design and Phytomedicine

 
Dr Marissa  Balmith
https://orcid.org/0000-0002-9209-7318
Dr Brian Flepisi
https://orcid.org/0000-0002-0628-4636
 

Research Leaders: Dr Marissa Balmith and Dr Brian Flepisi

CANCER METASTASIS - TARGETING THE CYTOSKELETON

It is well established that cancer is daunting in the breadth and scope of its diversity, spanning genetics, cell and tissue biology, pathology, and its response to therapy. Cancer cells are characterised by several hallmarks which include uncontrolled cellular proliferation, local invasion as well as the ability to spread to distant sites, in a process known as metastasis. Metastasis remains a challenge in terms of treatment and is usually the primary cause of morbidity and mortality in cancer patients, accounting for 90% of cancer related deaths. Thus, there is an urgent need for new drugs for treatment and or prevention of cancer metastasis. The cytoskeleton, a highly organised network of intracellular filaments, plays a crucial role in regulating cell shape, division, functions, and interactions within human organs and tissues. However, when this intricate network becomes dysregulated, it can contribute to various human diseases, including cancer. Our research aims to elucidate the functions of the cytoskeleton, its involvement in cancer progression and understanding the mechanisms underlying cytoskeletal regulation by exploring microfilament (actin cytoskeleton), microtubule (β-tubulin), and intermediate filament (vimentin, keratins, cytokeratins, and lamins) structures. Our research aims to alleviate the cancer-disease burden by investigating the role of the cytoskeleton in metastatic breast cancer cell lines using in silico and in vitro approaches. Cytoskeletal components mediating metastasis will be identified and their expression levels elucidated. Thereafter, the cytotoxicity of inhibitors will be determined against these targets by selecting inhibitors of those functions.

Collaborators:  Prof Joji (Anne) Mercier (Physiology, University of Pretoria), Dr Pontsho Moela (Biochemistry, Genetics and Microbiology), Dr Max Wicha (Internal Medicine, University of Michigan), Ms Margo Nell (Pharmacology, University of Pretoria)

Applicable research levels: Basic sciences research at Hons, MSc, or PhD level

Minimum skillsets at MSc and PhD levels: Cell culture (most preferred), spectrometric methods, microscopy (light and fluorescence), Western blotting, confocal microscopy and/or migration/invasion assay, and/or flow cytometry

Students: Mr Darren Chetty (MSc candidate); Vacancy available

IN SILICO MOLECULAR MODELLING AND DRUG DESIGN: TARGETING CANCER METASTASIS

The use of in silico tools provide the ideal platform in providing a deeper underlying understanding of the interactions of highly expressed cytoskeletal proteins for the discovery and identification of novel inhibitors for cancer metastasis. Our research scope covers a wide range of computational and molecular modelling research areas with focus on biological systems and drug design approaches. The main interest of our research is related to the design and study of biologically and therapeutically oriented targets by employing the applications of computational methods to the study of problems of chemical and biochemical reactivity. This includes mechanistic pathways, design of enzyme inhibitors and exploring the binding and catalytic theme of the designed targets and adopting sophisticated computational approaches to understand protein structures and functions.

Collaborators: Dr Krishna Govender (University of Johannesburg), Dr Tharindu Senapathi (Chemistry, University of Sri Jayewardenepura)

Applicable research levels: In silico research at Hons, MSc, or PhD level

Minimum skillsets at MSc and PhD levels: Virtual screening, molecular docking, molecular dynamic simulations, pharmacophore mapping, QM/MM simulations

Students:  Vacancy available

Resources: https://pubmed.ncbi.nlm.nih.gov/27637475/

https://link.springer.com/article/10.1515/biolog-2017-0012

https://pubs.rsc.org/en/content/articlelanding/2017/mb/c6mb00803h

https://pubmed.ncbi.nlm.nih.gov/28144904

THE EFFECT OF PHYTOMEDICINE ON CANCER METASTASIS

Phytomedicine has become an area of great interest in cancer research, particularly in understanding the mechanisms involved in metastasis. Recent studies have unveiled the potential of phytochemicals including flavonoids, polyphenols, and alkaloids in suppressing cancer cell migration, invasion, and metastatic colonisation. Thus, our research study aims to determine the in vitro effects of selected plant extracts or isolated phytochemicals on breast cancer cell lines with the aim of inhibiting metastasis.

Collaborators: Prof Vinesh Maharaj (Department of Chemistry, University of Pretoria), Ms Petunia Degashu (Department of Pharmacology, University of Pretoria)

Applicable research levels:  Basic sciences research at MSc and PhD level

Minimum skillsets at MSc level:  Plant extraction, fractionation, cell culture, cytotoxicity testing, microscopy (light and fluorescence), confocal microscopy Western blotting, flow cytometry, LC/MS-MS

Students:  Vacancy available

 

 

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