Can slight variations in lab environments affect the malaria-causing parasite (Plasmodium) and its tolerance to anti-malarial drugs? Griffith University’s Sandra Duffy believes it’s possible.
The PhD candidate in Discovery Biology at the Griffith Institute for Drug Discovery (GRIDD) was invited to write an opinion piece on the subject with GRIDD Principal Research Leader Professor Vicky Avery, who had previously been approached by a reputable journal to explore the topic of best practices for anti-parasitic drug discovery, focusing on malaria.
Routine in vitro culture of Plasmodium falciparum: experimental consequences? published in the latest issue of Trends in Parasitology, is based on Ms Duffy’s observations of the documented variations in culturing the malaria-causing parasite in humans (Plasmodium falciparum) during a decade of work at Griffith.
Having started her PhD in late 2017 to expand her career horizons within an academic setting, Ms Duffy narrowed her PhD focus to an issue that had plagued her years in the lab: variable parasite behaviour and what made them behave this way.
“Throughout my 10 years working within malaria drug discovery and culturing the Plasmodium parasite in the lab, I noticed inconsistent parasite behaviour, either associated with their growth or sensitivity to various drugs, which made me question what made them behave this way,” Ms Duffy said.
“In a lab performing the work we do for drug discovery programmes, it is essential to have uniform, reproducible data which we work hard to maintain by employing best practices at every level of our research.
“With so many questions in the back of my mind and not all the answers I wished for, the obvious PhD project for me was to investigate why we sometimes see these differences in how the parasite is growing and the consequences in relation to experimental outcomes.”
When Professor Avery was approached by Trends in Parasitology to write the opinion piece, she said Ms Duffy was a natural choice to co-author it as her research work was highly relevant to the proposed topic.
Professor Avery also highlighted that Ms Duffy was the only recipient in Australia of the prestigious NHMRC Postgraduate Dora Lush Scholarship, and only one of two Queensland higher degree by research students to receive any of the NHMRC Postgraduate scholarships for 2018.
“It’s an outstanding achievement illustrating the high calibre research contributions that Ms Duffy has and will undoubtedly continue to undertake throughout her research career,” Professor Avery said.
“The implications of Ms Duffy’s observations that the conditions under which the malaria-causing parasite is cultured can impact on research outcomes has far reaching implications. A consequence may be skewed interpretation of results by the variations she has documented, thus misdirection, which in turn could affect the way anti-malaria drugs are selected and developed.”
Ms Duffy said artemisinin is currently employed as the gold standard drug of choice by the World Health Organisation, which is used in a combination with other anti-malarial drugs, but resistance is being demonstrated, not only to the partner drugs with which artemisinin is combined, but artemisinin itself.
“If these drug combinations were to fail outright and resistant parasites spread to Africa, then so many lives could be lost,” Ms Duffy said.
“After a trip to Ghana and seeing things close up, malaria the disease became much more real to me. It is now not just a ‘parasite’ growing in a petri dish in the lab.”
Abstract of Routine in vitro culture of Plasmodium falciparum: experimental consequences?
The advent of Plasmodium falciparum (Pf) in vitro culturing opened the door for malaria research, yielding dramatic advancements in our understanding of the parasite. However, fundamental foundations taken for granted in our research endeavours can sometimes unknowingly be an Achilles heel, resulting in misleading outcomes and thus potential misdirection. In relation to malaria research, this could be our non-questioning acceptance of “routine in vitro culture of Pf”. In reality, there is nothing routine or straightforward regarding the dynamic and intimate relationship between the parasite and the in vitro environment. Here, we discuss recent studies demonstrating the impact slight variations in in vitro Pf culture parameters can have on scientific conclusions. We reason that culture conditions should be re-established as a primary consideration in in vitro malaria experimentation.
Routine In Vitro Culture of Plasmodium falciparum: Experimental Consequences?
Duffy S, Avery VM.
Trends Parasitol. 2018 May 22. pii: S1471-4922(18)30087-4. doi: 10.1016/j.pt.2018.04.005. [Epub ahead of print] Review.