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Biology subjects

Filipovic, I.

Publications and source records attributed to Filipovic, I..

3 recordsLinked to original sources

Molecular definition of group 1 innate lymphoid cells in the mouse uterus

Determining the function of uterine lymphocytes is challenging because of the rapidly changing nature of the organ in response to sex hormones and, during pregnancy, to the invading fetal trophoblast cells. Here we provide the first genome-wide transcriptome atlas of mouse uterine group 1 innate lymphoid cells (g1 ILCs) at mid-gestation. The composition of g1 ILCs fluctuates throughout reproductive life, with Eomes-veCD49a+ ILC1s dominating before puberty and specifically expanding in second pregnancies, when the expression of CXCR6, a marker of memory cells, is upregulated. Tissue-resident Eomes+CD49a+ NK cells (trNK), which resemble human uterine NK cells, are most abundant during early pregnancy, and showcase gene signatures of responsiveness to TGF-{beta}, connections with trophoblast, epithelial, endothelial and smooth muscle cells, leucocytes, as well as extracellular matrix. Unexpectedly, trNK cells express genes involved in anaerobic glycolysis, lipid metabolism, iron transport, protein ubiquitination, and recognition of microbial molecular patterns. Conventional NK cells expand late in gestation and may engage in crosstalk with trNK cells involving IL-18 and IFN-{gamma}. These results identify trNK cells as the cellular hub of uterine g1 ILCs at mid-gestation and mark CXCR6+ ILC1s as potential memory cells of pregnancy.

immunology

Improved Aedes aegypti mosquito reference genome assembly enables biological discovery and vector control

Female Aedes aegypti mosquitoes infect hundreds of millions of people each year with dangerous viral pathogens including dengue, yellow fever, Zika, and chikungunya. Progress in understanding the biology of this insect, and developing tools to fight it, has been slowed by the lack of a high-quality genome assembly. Here we combine diverse genome technologies to produce AaegL5, a dramatically improved and annotated assembly, and demonstrate how it accelerates mosquito science and control. We anchored the physical and cytogenetic maps, resolved the size and composition of the elusive sex-determining \"M locus\", significantly increased the known members of the glutathione-S-transferase genes important for insecticide resistance, and doubled the number of chemosensory ionotropic receptors that guide mosquitoes to human hosts and egg-laying sites. Using high-resolution QTL and population genomic analyses, we mapped new candidates for dengue vector competence and insecticide resistance. We predict that AaegL5 will catalyse new biological insights and intervention strategies to fight this deadly arboviral vector.

genomics

Fine-scale landscape genomics of Aedes aegypti reveals loss of Wolbachia transinfection, dispersal barrier and potential for occasional long distance movement

The endosymbiotic bacterium Wolbachia suppresses the capacity for arboviral transmission in the mosquito Aedes aegypti, and can spread through wild mosquito populations following local introductions. Recent introductions in Cairns, Australia have demonstrated slower than expected spread, that could be due to: i) barriers to Ae. aegypti dispersal; ii) leptokurtically distributed dispersal distances; and iii) intergenerational loss of Wolbachia. We investigated these three potential causes using genome-wide single-nucleotide polymorphisms (SNPs) and an assay for the Wolbachia infection wMel in 161 Ae. aegypti collected from Cairns in 2015. We observed a significant barrier effect of Cairns highways on Ae. aegypti dispersal using distance-based redundancy analysis and patch-based simulation analysis. We detected putative full-siblings in ovitraps 1312m apart, suggesting long-distance female movement likely mediated by human transport. Finally, we found a pair of full-siblings of different infection status, suggesting loss of Wolbachia in the field. While the long-distance movement and Wolbachia loss currently represent single observations, these findings together with the identified dispersal barriers can contribute to the slow spread of Wolbachia through the Ae. aegypti population in Cairns. Our landscape genomics approach can be extended to other host/symbiont systems that are being considered for biocontrol.

ecology