Impact of Biochemistry and Molecular Biosciences on Vector-Borne Diseases

Climate change is causing a shift in the population distributions of living organisms, including disease-carrying ones; an example being mosquitoes which are responsible for transmitting diseases such as dengue fever, malaria, and West Nile virus. Biochemistry is the study of the chemical reactions within living organisms, and more generally, molecular biosciences are the study of the molecules and chemicals and their interactions within cells and living organisms. This report explores how biochemistry and molecular biosciences can contribute to addressing the threat posed by mosquitoes and the diseases they transmit.

Introduction

Vector-borne parasite diseases have always been influenced by many social and economic factors. The mounting impact that climate change has on the environment, in addition to its influence on the triggering pathogens, is now becoming more understood as areas of the globe become much hotter, providing favorable and stable ecosystems for disease-carrying organisms to thrive.

One of the most prolific of these parasite diseases is malaria, caused by female Anopheles mosquitoes, that transmit the parasite into the host’s blood via a bite (blood feeding).

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Their saliva contains the genus Plasmodium species of parasite, which enters the liver through the bloodstream whereupon it differentiates and reproduces asexually in the liver cells. They re-enter the bloodstream, specifically the red blood cells, where again they multiply and grow until the cells burst, releasing them back into the cycle again.

The nature of this parasite allows it to go undetected by the body’s immune system, bypassing several key responses when a foreign agent is usually identified by the immune system.

Due to these intelligent methods, malaria can often go undetected or undiagnosed as many of the symptoms can be attributed to common colds and fevers caused by different pathogens. In some cases, even death can occur if not identified or treated properly.

Several biochemical techniques have been utilized at the forefront of the control strategies currently being implemented around the world in order to help diagnose malaria infections (rapid diagnostic tests, microscopy, and PCR testing), in addition to helping identify which strain of the disease the patient may have.

In contrast, new research and technological advancements in molecular bioscience have started to demonstrate a possible pathway to combat the very biology of the organisms responsible for the spread of parasitic diseases.

Body

Gene drive systems are a molecular bioscience technique that permits a desired gene (either positive or negative) to be purposefully spread throughout a species wild population, far quicker than through natural reproduction. Research has determined that the CRISPR-Cas9 gene drive system allowed for the potential to diminish the reproductive abilities of mosquitoes by re-engineering homing endonuclease genes (HEGs) within a caged population. They identified three genes (AGAP005958, AGAP011377, and AGAP007280) that when disturbed, can bestow an observable sterility amongst female mosquitoes.

As demonstrated in Table 1, an elevated transmission rate of the CRISPRh allele with both male and female mosquitoes was observed, with more success happening from the use of AGAP011377 and AGAP007280.

By suppressing mosquito reproduction, you could potentially reduce mosquito populations across the globe by editing genes and customizing these primary vectors of the disease. By including such traits into a controlled male mosquito population, it can be theorized that gene drive systems could be used to spread the transgenes into the wild population through natural reproduction (^{Alphey, 2016}).

In another study, similar gene drive system methods were used to target the specific malaria-resistance trait in mosquitoes. Researchers developed a system called the mutagenic chain reaction (MCR) that can transmit a targeted recessive allele at a much higher rate than projected through Mendelian inheritance (^{Gantz and Bier, 2015}).

The data presented in Table 2 supports their theory that the allele exchange within germline and somatic lineages is possible using this MCR technique, achieving an average of 97% success rate in offspring presenting the y-phenotype.

Conclusion

Climate change creates an increased burden on society, despite increased methods to reduce the spread of disease. Biochemistry and molecular bioscience methods can have a huge impact on the fight against climate change and its impact on vector-borne diseases, both as a diagnostic tool and as a method to potentially edit the genetic nature of mosquitoes.

By intervening with the mosquito’s ability to reproduce, scientists have the potential to disrupt the life cycle of mosquitoes that is fundamental to both their survival and the transmission of the malaria disease across populations. Furthermore, controlling a mosquito’s ability to develop specific malaria-resistance traits could help eradicate the disease altogether.

With the increased threat of warmer, more favorable environments for disease-carrying organisms to migrate to, especially into regions previously safe from such infestations, it is vital that further research and funding can be used to create such innovative and ground-breaking techniques to help tackle this issue.

Unfortunately, such methods are currently extremely expensive and would require significant advances in infrastructure, legislation, and regulation for them to cause an impact on the larger mosquito populations. Additionally, there is potential for there to have a far greater conservational impact on mosquito species, unless a targeted genus approach is taken using these techniques (^{Alphey, 2016}).

Until this is achieved, these strategies, whilst pioneering, would not be practical at this time.

References

• Alphey, L. (2016). Can CRISPR-Cas9 gene drives curb malaria?. Nature Biotechnology, 34(2), 149-150.
• Gantz, V.M. and Bier, E. (2015). The mutagenic chain reaction: a method for converting heterozygous to homozygous mutations. Science, 348(6233), 442-444.
• Hammond, A., Galizi, R., Kyrou, K., Simoni, A., Siniscalchi, C., Katsanos, D., Gribble, M., Baker, D., Marois, E., Russell, S., Burt, A., Windbichler, N., Crisanti, A. and Nolan, T. (2016). A CRISPR-Cas9 gene drive system targeting female reproduction in the malaria mosquito vector Anopheles gambiae. Nature Biotechnology, 34(1), 78-83.
• Tuteja, R., (2007). Malaria – an overview. FEBS Journal, 274(18), 4670-4679.