Associate Professor of Immunology and Infectious Diseases
Member, Broad Institute
Associate Professor, University of Perugia, Italy
Malaria, a leading cause of death in tropical and subtropical regions, is transmitted by the bite of female Anopheles mosquitoes. In Africa, where 90% of deaths occur, the major malaria vector is the mosquito Anopheles gambiae. Females of this and related species have a high reproductive capacity that is ensured by a single mating event followed by multiple blood feeding cycles (Fig. 1).
|Figure 1. Anopheles gambiae mosquitoes during mating. The male mosquito on the left and a bloodfed female on the right. Photo courtesy of Sam Cotton UCL.|
In our research group we study the molecular and behavioral parameters that are key to the ability of Anopheles mosquitoes to transmit malaria, with special emphasis on reproductive biology and vector-Plasmodium interactions. Our aim is to provide crucial knowledge to aid the development of new, effective tools for mosquito and malaria control. A key component of our research includes fieldwork studies in Africa on mating biology and natural malaria infections. These studies, in collaboration with IRSS in Burkina Faso, ICIPE in Kenya and other partners, are expanding our understanding of mosquito reproductive biology, mosquito-microbiota interactions, and natural malaria infections.
Currently our scientific program covers a number of research areas:
Reproductive biology; genetic and evolutionary approaches to study reproductive traits important for vectorial capacity. Over the past few years we have been exploring previously unknown hormonal signalling pathways that are relevant for the reproductive success of the mosquito vector. We have demonstrated that the steroid hormone 20-hydroxyecdysone (20E), produced by the male and transferred to the female during mating as part of a coagulated mating plug, has dramatic effects on female physiology and behaviour. Sexual transfer of this hormone, an acquired trait in anopheline mosquitoes based on our evolutionary analyses, increases egg development after blood feeding, induces egg laying, helps fertility and triggers a long-lasting refractoriness to further copulation. We are currently characterizing the hormonal signaling pathways triggered by mating and boosted by blood feeding to study how the interplay between these two key reproductive processes determines female reproductive success in a number of mosquito species.
Mosquito pathways that facilitate Plasmodium development. While a wealth of studies have focused on the immune responses of mosquitoes to Plasmodium infections, little is known about how these parasites exploit the physiological environment of the blood-fed mosquito to develop and become transmissible, or how these unknown vector-parasite interactions may differ depending on the specific Anopheles–Plasmodium combination. We are studying the physiological factors that are exploited by Plasmodium parasites (P. falciparum and P. vivax) for their own development using a variety of mosquito species in combination with both laboratory and field isolates of human malaria parasites. Moreover, we aim to analyze the effects of novel control tools on the vectorial competence of Anopheles mosquitoes, and to determine selective pressures that may be imposed by these tools on Plasmodium parasites.
From the bench to the field: generation of tools to reduce the malaria burden. Our lab is strongly committed to developing translational tools to suppress field mosquito populations and prevent malaria transmission. Widespread insecticide resistance among Anopheles mosquito populations represents one of the most significant threats to existing malaria control programs. We aim to translate our laboratory findings into novel products that can aid current insecticide-based programs or provide effective alternatives to insecticide use. Our projects include the generation of gene drive systems to spread anti-Plasmodium genes through mosquito populations, the identification and validation of natural mosquito endosymbionts that prevent Plasmodium development, such as Wolbachia, and the generation of sterilizing and life-shortening compounds that can be incorporated into insecticide-based control programs.
Mitchell SN, Kakani EG, South A, Howell PI, Waterhouse RM, Catteruccia F. Mosquito biology. Evolution of sexual traits influencing vectorial capacity in anopheline mosquitoes. Science. 2015 Feb 27;347(6225):985-8. PubMed PMID:25722409.
Gabrieli P, Kakani EG, Mitchell SN, et al. Sexual transfer of the steroid hormone 20E induces the postmating switch in Anopheles gambiae. Proc Natl Acad Sci U S A. 2014 Nov 18;111(46). Epub 2014 Nov 3. PubMed PMID:25368171
Esvelt KM, Smidler AL, Catteruccia F, Church GM. Concerning RNA-guided gene drives for the alteration of wild populations. Elife. 2014 Jul 17:e03401. doi: 10.7554/eLife.03401. [Epub ahead of print] PubMed PMID:25035423
Baldini F, Segata N, Pompon J, Marcenac P, Robert Shaw W, Dabiré RK, Diabaté A, Levashina EA, Catteruccia F. Evidence of natural Wolbachia infections in field populations of Anopheles gambiae. Nat Commun. 2014 Jun 6;5:3985. PubMed PMID:24905191
Shaw WR, Teodori E, Mitchell SN, Baldini F, Gabrieli P, Rogers DW, Catteruccia F. Mating activates the heme peroxidase HPX15 in the sperm storage organ to ensure fertility in Anopheles gambiae. Proc Natl Acad Sci U S A. 2014 Apr 22; PubMed PMID: 24711401.
Ph.D. in Molecular Entomology, 1999, Imperial College London
Honors and Awards
MRC Career Development Award, 2006
Wellcome Trust Value in People Award, 2006