ISEV eNEWS Member Spotlight

Thabiso Motaung

Tell us a little about your EV research, what attracted you to this field and what are the biggest obstacles to your EV research? What are your thoughts on how ISEV might help to address any challenges?

My research on extracellular vesicles (EVs) is still in its early stages. As far as I recall, I first saw a paper about sRNAs packaged in EVs in 2019, just a few months after starting as a lecturer at the University of Pretoria's Department of Biochemistry, Genetics, and Microbiology. As part of my early career development program, I was working on a proposal to conduct small RNA research at the time. The study's overarching goal was to investigate the role of RNA interference in plant-pathogen interactions. This was part of an ongoing intervention at the Forestry and Agricultural Biotechnology Institute (FABI) aimed at developing sustainable control strategies for severe pine tree diseases caused by the fungal pathogen Fusarium cercinatum.

Subsequent to understanding the incredible capability of EVs to ship compounds including sRNAs, I immediately aligned my research with unpacking the obscure effects of EVs on the biology of forest pathogens and their hosts. I lead a few EV related projects including one on F. vertiticilliodes biofilm formation and mycotoxin production. The biofilm component is also part of the F. cercinatum project, and is specifically focused on characterizing Fusarium EVs released by planktonic and biofilm cells, to determine the cargo differences from EVs released by these cell types and their influence on host immune response against the pathogen.

My research group is also interested in charactering vesicles from trees such as species from the genus Pinus, and the subsequent uptake of pine-derived EVs by fungal cells. The associated physiological effects on fungi are at present evaluated in an assortment of ways, including through OmniLog Phenotypic Microarrays of the fungal pathogen following its exposure to host EVs. My research is supported by the National Research Foundation of South Africa and is currently being carried out by masters and doctoral students. The ultimate goal of my vesicle research is to use EVs to biologically control pathogens and/or as a biomarker and diagnostic tool for plant infectious diseases.

Many of the difficulties we've encountered as a group thus far have been related to a lack of research funds. International grants are difficult to obtain and frequently require someone to be established in their field or collaborate with experts across the border, but this comes with connections, which a small research group working on a relatively new field does not yet have. This is where I believe ISEV can help, because it brings together a global network of EV researchers under one topic.

What more do you think ISEV could support the global network of EV researchers?

In my humble opinion, the current representation of the EV research community within ISEV could be more diverse in terms of the areas of research that EVs fit into, including plant science and microbiology domains. When you look at the board of directors, for example, you will notice that scientists who are interested in the medical/clinical aspects of EVs are well represented, relative to others. ISEV assumes a vital role in supporting researchers across all fields of EV research. As a result, having strong representation within this community that is consistent with diverse EV research areas will empower the global network of EV researchers.

Do you plan to continue with EV research in the future and if so, what questions would you like to pursue?

We know very little about microbial functionality in extreme environments although it may be highly relevant to 21st century agricultural challenges. Such unleveraged potential can be implemented to improve soil fertility, boost plant tolerance to various environmental stresses, and raise agricultural output, all while benefiting human health and providing enough food for a growing human population in an environmentally acceptable manner. Microbes living at extremes, however, are profoundly adjusted to extreme conditions, making them difficult to maintain and investigate in the lab. Therefore, in the future, a part of my EV research will focus on determining how EVs can be used to tap into the biotechnological importance of extremophilic microbes. This is based on the assumption that all living microbes continuously release a fleet of EVs into their environment in order to modify (optimize) it for survival and growth. Furthermore, current methods permit the isolation of EVs from nearly any source, implying that even EVs released into the environment by extremophilic microbes can be isolated and studied and or optimised for exogenous use, allowing for easy modification and direct discovery of biotechnologically relevant, microbial community produced, bioactive compounds.

How do you see your career progressing over the next five to ten years?

I envision that a number of PhDs and postdocs from my research group should be well trained in the field of EVs, which will significantly boost the EV research capacity in South Africa and Africa as a whole. This will also elevate me to the ranks of one of the leading researchers in this field. There is currently very little research on EVs in Africa, and I am concerned that we are missing out on being a part of a movement aiming to put vesicles into good use for the benefit of society. I'm also hoping that as capacity in the EV research space grows, South Africa will be able to host a scientific meeting focused solely on EVs, under the auspices of the South African Society of EVs (SASEV). In the next five years, I want to see my research also contributing towards achieving this goal.

In what way have collaborations with other groups or with industry impacted on your EV studies?

Positively. As a result, my research on EVs is venturing into other areas, opening up new opportunities for growth. My research group, for example, is working on a project to characterize the potential of EVs derived from microbial fungal endophytes found in medicinal plants grown in the Limpopo province (South Africa). This study is important because medicinal plants contain a wealth of biologically active compounds that can be used to treat a wide range of chronic and infectious diseases. Some of these medically relevant compounds are likely concentrated inside the EVs of these plants. Furthermore, South Africa is rich not only in the variety of medicinally significant plants, but also in the knowledge of how to use them. For these reasons, investigating the therapeutic potential of EVs derived from medicinal plants is a fascinating prospect. My group is also planning a collaboration on a project to isolate and characterize EVs from South Atlantic marine microbes (bacteria, archaea, and fungi). This work is geared towards enhancing knowledge on microbial responses to environmental changes in a marine setting and to evaluate their likely potential to alter ecosystem services.

Did you go to ISEV2021 or to any other recent meeting in which EV research was discussed and if so, what was a highlight for you?

I have not yet attended an ISEV meeting. However, I hope that in the not-so-distant future, most likely at the ISEV annual meeting in 2023, my students and I will showcase some of the key findings emanating from research on EVs. For the time being, I will participate in the upcoming Fungal Genetics Conference, which will be held in March this year in California.

In-San Kim

Tell us a little about your EV research, what attracted you to this field and what are the biggest obstacles to your EV research?  What are your thoughts on how ISEV might help to address any challenges? 

I started to study exosomes when I saw the potential to overcome limitations in current drug modalities. Many of ‘undruggables' are intracellular and require larger molecules such as proteins. EVs can be functionalized to deliver theselarger therapeutics into cells. Furthermore, exosomes can carry multiple functions to have better biocompatibility, biodistribution, and multiple payloads. Therefore, exosomes are a strong candidate for the next generation drug modality.

We have to ask how to efficiently load large proteins including membrane proteins and nuclear proteins, or nucleic acids into exosomes, for most undruggable targets exist inside cells. TheISEV community should actively discuss fundamental research on the biogenesis of exosomes and how specific substances are imported into them.

What more do you think ISEV could do to support the global network of EV researchers?

EVs and EV-based therapeutics have gained much attention and appreciation as a novel effective treatment method in the last decade through ISEV's endeavors. I hope ISEV will support the establishment of programs and networks that can promote translational research by expanding its global network with the leading scientists working in the field.

Do you plan to continue with EV research in the future and if so, what questions would you like to pursue?

I am certainly planning to continue with EV research in the future. I believe exosomes have the potential to be the next-generation drug modality, and it will be essential to study the biogenesis of exosomes and the sorting of specific substances into exosomes. Considering that diseases are complex, heterogenous, and polygenic, pathophysiological roles of EVs in the development of such complex chronic diseases should be more comprehensively understood.

How do you see your career progressing over the next five to ten years?

In the next ten years, I plan to continue research on exosomes and dedicate my endeavors to developing exosome therapeutics and bench-to-bedside research of exosomes.

In what way have collaborations with other groups or with industry impacted on your EV studies?

In the future, I wish to collaborate with other groups or industries if the interests align and believe that ISEV will play a vital role by supporting networks and promoting collaborations on EV studies.  I am currently working on research and technology commercialization through start-up companies and this interaction has dramatically impacted my EV research.

Did you go to ISEV2021 or to any other recent meeting in which EV research was discussed and if so, what was a highlight for you?

It is unfortunate that we have not been able to communicate with ISEV members in person due to the recent pandemic. I am very much looking forward to interacting with ISEV more in 2022.