By Ebele Orakpo
It was Dr. Alex Marvel, a clinical psychologist who said that when you start looking for solutions to your problems in others, you will not find them because they are within yourself. This holds true for Africa, the answer to the continent’s myriad problems lies in the hands of her citizens.
This saying must have propelled a team of researchers led by Professor Ezekiel Femi Adebiyi, Head, Department of Computer and Information Sciences, College of Science and Technology and Lead, Bioinformatics Research, Covenant University, Ota, to go into research work aimed at not just reducing malaria transmission to a level where it is no longer a public health problem, but eradicating it altogether by turning theories to products. He spoke to Vanguard Learning via e-mail. Excerpts:
Eradication developments for the decade
According to Professor Ezekiel Adebiyi, the overall goal of the project which is in three phases “is to produce effective three high tech products for the control and final eradication of malaria starting with Nigeria. The malaria parasite needs man and the mosquito to continue surviving.”
Elaborating, Professor Adebiyi who is the President, Nigeria Society of Bioinformatics and Computational Biology, and Secretary, African Society of Bioinformatics and Computational Biology, said; “Our first targeted product (from project I), a cuisine of anti-malaria drugs, is to allow rapid cure of malaria in humans.
This is to reduce to zero the chance of an uninfected mosquito being infected after a bite. The second targeted product (from project II), an advanced but human-friendly pesticide, is to help delete rapidly all malaria infected mosquitoes.
The third (from project III) is aimed at producing a mathematical modelling for the prediction of mosquitoes’ metapopulation dynamics towards understanding and validating the seasonal dynamics of this vector. An integration of novel genetic control methods such as Sterile Insect Technique (SIT), lethal densovirus and genetically manipulated endopathogenic fungi, into this mathematical modelling, will allow us to push down the population of the mosquitoes in some areas as may be necessary during the deployment phase of the first two products.”
Where are we presently/ Novel finding:
Adebiyi said that as touching project I, “a computational method (popularly called CPA) investigating the topology of the biochemical metabolic networks was developed to mine new viable drug targets in the most deadly malaria parasite, Plasmodium falciparum.
Initial drug screening in-vitro anti-plasmodial assay experiments in Prof. Michael Lanzer’s laboratory at the University of Heidelberg, Germany have been performed against the predicted drug targets. The results obtained have been successful on some of the enzymatic sites and it shows that the predicted sites on the malaria parasite proved to be effective as drug targets.
For the first time, this work may produce novel anti-malarial drugs, whose biological mode of action can be determined accurately. This is a novel finding as the biological mode of action of even the most efficient anti-malarial drug is presently unknown. This discovery provides for the first time anti-malarial drug target sites upon which a viable structural design pipeline is being built.
It also provides a viable platform to optimize the fitting of `indigenous’ medicinal plants’ bioactive compounds via a rational drugs design approach. Further pre-clinical development is on-going to design and take successful inhibitors (drugs) to the market,” he said, adding; “the execution of this pre-clinical development will cost 2.5 – 3m Euro. This cost will be borne with other funding bodies and our industry partners. Covenant University has provided an initial fund of about 104,000 Euro to jump-start this.”
Speaking on project II, Adebiyi said; “The overall goal is to produce evolution-proof insecticides that will only kill malaria-infected Anopheles gambiae (A. gamb) mosquitoes. Strong non-genomics rationals behind such innovation have been carefully enumerated in a PLoS Essay by Read, Lynch and Thomas entitled: How to make evolution-proof insecticides for malaria control.
“In a work I did with Dr Olubanke Ogunlana of the Department of Biological Sciences, Covenant University, a first version of biochemical metabolic network, AnoCyc, for A. gambiae was developed and deployed under the www.bioCyc.org databases. This will enable us to extract effectively, insecticidal targets upon which to build the first generation of evolution-proof insecticides.”
For project III, Adebiyi said a C++ based, stochastic spatially-explicit predictive computational model (AnoSpEx) has been developed, which is “biologically rich, weather data-driven, and parameterized by field data, to simulate Anopheles metapopulation dynamics towards understanding and validating the seasonal dynamics of this vector.
The next research is to develop an advanced model by integrating novel genetic control methods into AnoSpEx. This will be realised by incorporating genetic concepts such as SIT (Sterile Insect Technique), lethal densovirus and genetically manipulated endo-pathogenic fungi.”
Hand-held machine for detecting malaria infection at the liver stage:
Said Adebiyi; “From the understanding of our environment, in particular West Africa, it is perhaps the place where malaria originated and from the weather set-up, it will continue to be a reservoir of mosquitoes. We have a project geared at creating a technology (a hand-held machine) that will allow us to detect malaria infection at the liver stage.
The malaria parasite goes through the liver before arriving at the blood stage where it manifests. It is, therefore, imperative to note that many lives (in particular the people with sickle cell anaemia) will be saved if these parasites can be detected and treated at the asymptomatic liver stage instead of waiting till the disease manifestation at the blood stage.
Notwithstanding the importance of early and accurate diagnosis in malaria treatment discovery, most of the existing diagnostics gave little attention to malaria detection at the liver stage, hence the need to explore detection at this level of the parasite life cycle,” he said, noting that they have developed computational systems biology techniques that have been used to mine viable genes that can be used to develop Polymerase chain reaction (PCR) experiments for the detection of malaria at the liver stage. Our next task here is the development of PCR experimental protocols to experimentally validate the sensitivity of these genes.”
He said the anticipated hand-held machine will be useful to “save persons from the manifestation of malaria (even before we start our malaria eradication campaign) and this will be an advantage for persons with sickle cell anaemia. The results of this work will also be useful for the development of a viable anti-malaria vaccine.
One big plus of this project is that it will be very useful for sustenance of the gains obtained after the successful deployment of the Code Malaria technologies. That is, we are able to treat persons of malaria before the parasite enters the blood stage where the mosquito transmits it.
“The expected result of the successful execution and application of our work will make Nigeria and eventually, Africa, free of malaria-infected humans and mosquitoes like the western world,” he stated.