Bio

Dr Rosaline Macharia

Areas of specialization:
Genomics & Bioinformatics

Research Interests:
Comparative genomics, Data mining, One health, Food-security

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Rosaline's Resume

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Publications


2021

Mwangi, KW, Macharia RW, Bargul JL.  2021.  Gene co-expression network analysis of Trypanosoma brucei in tsetse fly vector., 2021 Jan 22. Parasites & vectors. 14(1):74. Abstract

Trypanosoma brucei species are motile protozoan parasites that are cyclically transmitted by tsetse fly (genus Glossina) causing human sleeping sickness and nagana in livestock in sub-Saharan Africa. African trypanosomes display digenetic life cycle stages in the tsetse fly vector and in their mammalian host. Experimental work on insect-stage trypanosomes is challenging because of the difficulty in setting up successful in vitro cultures. Therefore, there is limited knowledge on the trypanosome biology during its development in the tsetse fly. Consequently, this limits the development of new strategies for blocking parasite transmission in the tsetse fly.

2020

Koyaweda, GW, Ongus JR, Machuka E, Juma J, Macharia R, Komas NP, Pelle R.  2020.  Detection of circulating hepatitis B virus immune escape and polymerase mutants among HBV-positive patients attending Institut Pasteur de Bangui, Central African Republic., 2020 Jan. International journal of infectious diseases : IJID : official publication of the International Society for Infectious Diseases. 90:138-144. Abstract

Previous studies in the Central African Republic (CAR) have reported the presence of hepatitis B virus (HBV) recombinant genotype E/D and a suspicion of immune escape mutants (IEMs), without further investigation into their impact on prevention and diagnosis. Consequently, this study investigated HBV mutations among hepatitis B surface antigen (HBsAg)-positive patients attending Institut Pasteur de Bangui in the CAR.

Kabaka, JM, Wachira BM, Mang'era CM, Rono MK, Hassanali A, Okoth SO, Oduol VO, Macharia RW, Murilla GA, Mireji PO.  2020.  Expansions of chemosensory gene orthologs among selected tsetse fly species and their expressions in Glossina morsitans morsitans tsetse fly., 2020 06. PLoS neglected tropical diseases. 14(6):e0008341. Abstract

Tsetse fly exhibit species-specific olfactory uniqueness potentially underpinned by differences in their chemosensory protein repertoire. We assessed 1) expansions of chemosensory protein orthologs in Glossina morsitans morsitans, Glossina pallidipes, Glossina austeni, Glossina palpalis gambiensis, Glossina fuscipes fuscipes and Glossina brevipalpis tsetse fly species using Café analysis (to identify species-specific expansions) and 2) differential expressions of the orthologs and associated proteins in male G. m. morsitans antennae and head tissues using RNA-Seq approaches (to establish associated functional molecular pathways). We established accelerated and significant (P<0.05, λ = 2.60452e-7) expansions of gene families in G. m. morsitans Odorant receptor (Or)71a, Or46a, Ir75a,d, Ionotropic receptor (Ir) 31a, Ir84a, Ir64a and Odorant binding protein (Obp) 83a-b), G. pallidipes Or67a,c, Or49a, Or92a, Or85b-c,f and Obp73a, G. f. fuscipes Ir21a, Gustatory receptor (Gr) 21a and Gr63a), G. p. gambiensis clumsy, Ir25a and Ir8a, and G. brevipalpis Ir68a and missing orthologs in each tsetse fly species. Most abundantly expressed transcripts in male G. m. morsitans included specific Or (Orco, Or56a, 65a-c, Or47b, Or67b, GMOY012254, GMOY009475, and GMOY006265), Gr (Gr21a, Gr63a, GMOY013297 and GMOY013298), Ir (Ir8a, Ir25a and Ir41a) and Obp (Obp19a, lush, Obp28a, Obp83a-b Obp44a, GMOY012275 and GMOY013254) orthologs. Most enriched biological processes in the head were associated with vision, muscle activity and neuropeptide regulations, amino acid/nucleotide metabolism and circulatory system processes. Antennal enrichments (>90% of chemosensory transcripts) included cilium-associated mechanoreceptors, chemo-sensation, neuronal controlled growth/differentiation and regeneration/responses to stress. The expanded and tsetse fly species specific orthologs includes those associated with known tsetse fly responsive ligands (4-methyl phenol, 4-propyl phenol, acetic acid, butanol and carbon dioxide) and potential tsetse fly species-specific responsive ligands (2-oxopentanoic acid, phenylacetaldehyde, hydroxycinnamic acid, 2-heptanone, caffeine, geosmin, DEET and (cVA) pheromone). Some of the orthologs can potentially modulate several tsetse fly species-specific behavioral (male-male courtship, hunger/host seeking, cool avoidance, hygrosensory and feeding) phenotypes. The putative tsetse fly specific chemosensory gene orthologs and their respective ligands provide candidate gene targets and kairomones for respective downstream functional genomic and field evaluations that can effectively expand toolbox of species-specific tsetse fly attractants, repellents and other tsetse fly behavioral modulators.

2019

Attardo, GM, Abd-Alla AMM, Acosta-Serrano A, Allen JE, Bateta R, Benoit JB, Bourtzis K, Caers J, Caljon G, Christensen MB, Farrow DW, Friedrich M, Hua-Van A, Jennings EC, Larkin DM, Lawson D, Lehane MJ, Lenis VP, Lowy-Gallego E, Macharia RW, Malacrida AR, Marco HG, Masiga D, Maslen GL, Matetovici I, Meisel RP, Meki I, Michalkova V, Miller WJ, Minx P, Mireji PO, Ometto L, Parker AG, Rio R, Rose C, Rosendale AJ, Rota-Stabelli O, Savini G, Schoofs L, Scolari F, Swain MT, Takáč P, Tomlinson C, Tsiamis G, Van Den Abbeele J, Vigneron A, Wang J, Warren WC, Waterhouse RM, Weirauch MT, Weiss BL, Wilson RK, Zhao X, Aksoy S.  2019.  Comparative genomic analysis of six Glossina genomes, vectors of African trypanosomes., 2019 09 02. Genome biology. 20(1):187. Abstract

Tsetse flies (Glossina sp.) are the vectors of human and animal trypanosomiasis throughout sub-Saharan Africa. Tsetse flies are distinguished from other Diptera by unique adaptations, including lactation and the birthing of live young (obligate viviparity), a vertebrate blood-specific diet by both sexes, and obligate bacterial symbiosis. This work describes the comparative analysis of six Glossina genomes representing three sub-genera: Morsitans (G. morsitans morsitans, G. pallidipes, G. austeni), Palpalis (G. palpalis, G. fuscipes), and Fusca (G. brevipalpis) which represent different habitats, host preferences, and vectorial capacity.

2017

Mogire, RM, Akala HM, Macharia RW, Juma DW, Cheruiyot AC, Andagalu B, Brown ML, El-Shemy HA, Nyanjom SG.  2017.  Target-similarity search using Plasmodium falciparum proteome identifies approved drugs with anti-malarial activity and their possible targets., 2017. PloS one. 12(10):e0186364. Abstract

Malaria causes about half a million deaths annually, with Plasmodium falciparum being responsible for 90% of all the cases. Recent reports on artemisinin resistance in Southeast Asia warrant urgent discovery of novel drugs for the treatment of malaria. However, most bioactive compounds fail to progress to treatments due to safety concerns. Drug repositioning offers an alternative strategy where drugs that have already been approved as safe for other diseases could be used to treat malaria. This study screened approved drugs for antimalarial activity using an in silico chemogenomics approach prior to in vitro verification. All the P. falciparum proteins sequences available in NCBI RefSeq were mined and used to perform a similarity search against DrugBank, TTD and STITCH databases to identify similar putative drug targets. Druggability indices of the potential P. falciparum drug targets were obtained from TDR targets database. Functional amino acid residues of the drug targets were determined using ConSurf server which was used to fine tune the similarity search. This study predicted 133 approved drugs that could target 34 P. falciparum proteins. A literature search done at PubMed and Google Scholar showed 105 out of the 133 drugs to have been previously tested against malaria, with most showing activity. For further validation, drug susceptibility assays using SYBR Green I method were done on a representative group of 10 predicted drugs, eight of which did show activity against P. falciparum 3D7 clone. Seven had IC50 values ranging from 1 μM to 50 μM. This study also suggests drug-target association and hence possible mechanisms of action of drugs that did show antiplasmodial activity. The study results validate the use of proteome-wide target similarity approach in identifying approved drugs with activity against P. falciparum and could be adapted for other pathogens.

2016

Macharia, R, Mireji P, Murungi E, Murilla G, Christoffels A, Aksoy S, Masiga D.  2016.  Correction: Genome-Wide Comparative Analysis of Chemosensory Gene Families in Five Tsetse Fly Species., 2016 Dec. PLoS neglected tropical diseases. 10(12):e0005199. Abstract

[This corrects the article DOI: 10.1371/journal.pntd.0004421.].

Macharia, R, Mireji P, Murungi E, Murilla G, Christoffels A, Aksoy S, Masiga D.  2016.  Genome-Wide Comparative Analysis of Chemosensory Gene Families in Five Tsetse Fly Species., 2016 Feb. PLoS neglected tropical diseases. 10(2):e0004421. Abstract

For decades, odour-baited traps have been used for control of tsetse flies (Diptera; Glossinidae), vectors of African trypanosomes. However, differential responses to known attractants have been reported in different Glossina species, hindering establishment of a universal vector control tool. Availability of full genome sequences of five Glossina species offers an opportunity to compare their chemosensory repertoire and enhance our understanding of their biology in relation to chemosensation. Here, we identified and annotated the major chemosensory gene families in Glossina. We identified a total of 118, 115, 124, and 123 chemosensory genes in Glossina austeni, G. brevipalpis, G. f. fuscipes, G. pallidipes, respectively, relative to 127 reported in G. m. morsitans. Our results show that tsetse fly genomes have fewer chemosensory genes when compared to other dipterans such as Musca domestica (n>393), Drosophila melanogaster (n = 246) and Anopheles gambiae (n>247). We also found that Glossina chemosensory genes are dispersed across distantly located scaffolds in their respective genomes, in contrast to other insects like D. melanogaster whose genes occur in clusters. Further, Glossina appears to be devoid of sugar receptors and to have expanded CO2 associated receptors, potentially reflecting Glossina's obligate hematophagy and the need to detect hosts that may be out of sight. We also identified, in all species, homologs of Ir84a; a Drosophila-specific ionotropic receptor that promotes male courtship suggesting that this is a conserved trait in tsetse flies. Notably, our selection analysis revealed that a total of four gene loci (Gr21a, GluRIIA, Gr28b, and Obp83a) were under positive selection, which confers fitness advantage to species. These findings provide a platform for studies to further define the language of communication of tsetse with their environment, and influence development of novel approaches for control.

2015

Macharia, RW, Ombura FL, Aroko EO.  2015.  Insects' RNA Profiling Reveals Absence of "Hidden Break" in 28S Ribosomal RNA Molecule of Onion Thrips, Thrips tabaci., 2015. Journal of nucleic acids. 2015:965294. Abstract

With an exception of aphids, insects' 28S rRNA is thought to harbor a "hidden break" which cleaves under denaturing conditions to comigrate with 18S rRNA band to exhibit a degraded appearance on native agarose gels. The degraded appearance confounds determination of RNA integrity in laboratories that rely on gel electrophoresis. To provide guidelines for RNA profiles, RNA from five major insect orders, namely, Diptera, Hemiptera, Thysanoptera, Hymenoptera, and Lepidoptera, was compared under denaturing and nondenaturing conditions. This study confirmed that although present in most of insect's RNA, the "hidden break" is absent in the 28S rRNA of onion thrips, Thrips tabaci. On the other hand, presence of "hidden break" was depicted in whiteflies' 28S rRNA despite their evolutionary grouping under same order with aphids. Divergence of 28S rRNA sequences confirms variation of both size and composition of gap region among insect species. However, phylogeny reconstruction does not support speciation as a possible source of the hidden break in insect's 28S rRNA. In conclusion, we show that RNA from a given insect order does not conform to a particular banding profile and therefore this approach cannot be reliably used to characterize newly discovered species.

2014

International Glossina Genome Initiative.  2014.  Genome sequence of the tsetse fly (Glossina morsitans): vector of African trypanosomiasis., 2014 Apr 25. Science (New York, N.Y.). 344(6182):380-6. Abstract

Tsetse flies are the sole vectors of human African trypanosomiasis throughout sub-Saharan Africa. Both sexes of adult tsetse feed exclusively on blood and contribute to disease transmission. Notable differences between tsetse and other disease vectors include obligate microbial symbioses, viviparous reproduction, and lactation. Here, we describe the sequence and annotation of the 366-megabase Glossina morsitans morsitans genome. Analysis of the genome and the 12,308 predicted protein-encoding genes led to multiple discoveries, including chromosomal integrations of bacterial (Wolbachia) genome sequences, a family of lactation-specific proteins, reduced complement of host pathogen recognition proteins, and reduced olfaction/chemosensory associated genes. These genome data provide a foundation for research into trypanosomiasis prevention and yield important insights with broad implications for multiple aspects of tsetse biology.

Masiga, D, Obiero G, Macharia R, Mireji P, Christoffels A.  2014.  Chemosensory receptors in tsetse flies provide link between chemical and behavioural ecology., 2014 Sep. Trends in parasitology. 30(9):426-8. Abstract

Tsetse flies survive in a variety of environments across tropical Africa, often rising to large numbers, despite their low birth rate of one offspring every seven to nine days. They use olfactory receptors to process chemical signals in their environments to find food, escape from predators, and locate suitable larviposition sites. We discuss the identification of odorant and gustatory receptors in Glossina morsitans morsitans and the role genomics could play in management of nuisance insects.

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