- Author: Kathy Keatley Garvey
In humans, the disease is commonly known as sleeping sickness: the parasite invades the central nervous system and disrupts the sleep cycle. If not treated, the disease can result in progressive mental deterioration, coma, systemic organ failure and death.
The newly published research in the journal Genome Biology compares and analyzes the genomes of six species of tsetse flies and could lead to better insights into disease prevention and control. “It was a behemoth project, spanning six to seven years,” said Attardo, an assistant professor in the Department of Entomology and Nematology. “This project represents the combined efforts of a consortium of 56 researchers throughout the United States, Europe, Africa and China.”
Tsetse flies, Glossina sp., are of great medical and economic importance, wrote Attardo and co-authors Adly M. M. Abd-Alla of the Insect Pest Control Laboratory, Division of Nuclear Techniques in Food and Agriculture, Vienna, Austria, and Serap Aksoy of the Yale School of Public Health, New Haven, Conn. They related that since the implementation of surveillance and record-keeping in the 20th century, “millions of people in sub-Saharan Africa” have died from sleeping sickness.
Tsetse flies, which resemble house flies, are distinguished from other Diptera by unique adaptations, including lactation and the birthing of live young, a vertebrate blood-specific diet by both sexes, and obligate bacterial symbiosis. The scientists targeted 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.
“The aim of these studies,” the authors wrote, “was to generate and mine the genomic sequences of six species of tsetse flies with different ecological niches, host preferences, and vectorial capacities. The goals of the analyses performed here are to identify the novel genetic features specific to tsetse flies and to characterize the differences between the Glossina species to correlate the genetic changes with phenotypic differences in these divergent species.”
“Expanded genomic discoveries reveal the genetics underlying Glossina biology and provide a rich body of knowledge for basic science and disease control,” the scientists concluded. “They also provide insight into the evolutionary biology underlying novel adaptations and are relevant to applied aspects of vector control such as trap design and discovery of novel pest and disease control strategies.”
Attardo, who joined the UC Davis faculty in 2017 after serving 13 years with the Yale School of Public Health, said the massive research project involved “the complete sequencing and assembly of six Glossina species, including the two primary vectors of human African tryapnosomiasis, three major vectors of animal trypanosomiasis and one ancestral tsetse species which demonstrates some resistance to the species of trypanosomes responsible for human and some animal forms of the disease.”
The research, titled "Comparative Genomic Analysis of Six Glossina Genomes, Vectors of African Trypanosomes," offers:
- A clearer definition of the Glossina phylogenetic tree and placement of a controversial species.
- Identification of rapidly evolving regions of the tsetse genome relative to Drosophila.
- Identification of Glossina specific genes and their functions as well as expansions and contractions of gene families in tsetse relative to other flies.
“We discuss the functional implications of these changes and how they relate to tsetses' physiological adaptations and evolutionary history,” Attardo noted.
“We discovered that the rhodopsin gene family which is associated with vision/color detection shows conservation in motion detection and tracking associated genes.” Attardo said. “However, the gene coding for the protein that detects blue wavelengths is divergent relative to houseflies and shows the highest variance between Glossina species of all the rhodopsin genes. This is significant as the color blue is used as an attractant to bring tsetse into the traps used for control. It suggests that different species may be tuned/attracted to different wavelengths of blue.”
They also analyzed the genes associated with tsetse immunity and the relative differences in comparison with houseflies and fruit flies. “We see many immune genes missing in Glossina and increased copy numbers of genes associated with negative regulation of immune function. We think this may be associated with the evolution of obligate symbiosis as a way to protect their symbionts.”
“We also found extreme conservation of milk proteins between all sequenced species,” the UC Davis medical entomologist said. “On the flip side, male reproductive proteins (seminal proteins) appear to be very rapidly evolving relative to the rest of the genome. The copy numbers of these genes also change significantly between species.”
The scientists also found an overall reduction of olfactory associated genes and protein modifications specific to salivary proteins in the two species that vector human trypanosomiasis.
In 1995, the World Health Organization (WHO) estimated that 60 million people were at risk of sleeping sickness, with an estimated 300,000 new cases per year in Africa, and fewer than 30,000 cases diagnosed and treated. Due to increased control, only 3796 cases were reported in 2014, with less than 15,000 estimated cases, according to WHO statistics.
The parasitic disease “mostly affects poor populations living in remote rural areas of Africa,” according to WHO. “Untreated, it is usually fatal. Travelers also risk becoming infected if they venture through regions where the insect is common. Generally, the disease is not found in urban areas, although cases have been reported in suburban areas of big cities in some disease endemic countries.”
Several National Institutes of Health (NIH) grants, awarded to Attardo and Aksoy, funded the research. They also drew funding from the McDonnell Genome Institute at Washington University School of Medicine; the National Research Foundation, the Swiss National Science Foundation, and the Slovak Research and Development Agency.
- Author: Kathy Keatley Garvey
Attardo joined the department July 1 as an assistant professor after 13 years at the Yale University School of Public Health, New Haven, Conn., first as a postdoctoral fellow from 2004 to 2008, and then as associate research scientist and research scientist.
He now shares quarters in 37 Briggs Hall with Elina Lastro Niño, Extension apiculturist. Books on genes, genetics, genetic analysis, chemistry, biology and entomology line his book shelves, and macro images of insects and spiders brighten his walls. His coffee-table book, “Small World: Life Is in the Detail” showcases his passion for macro photography, particularly jumping spiders, dragonflies and praying mantids.
Geoffrey Attardo is eager to begin work. His research interests include the physiology and molecular biology of disease vectors, reproduction, nutrition, symbiosis, genetics, metabolomics, gene regulation, vector/parasite interactions “and any place the data leads me!”
“My lab will focus on aspects of the physiology of tsetse fly reproduction,” Attardo said. “The goal of this research is to identify and understand key aspects of tsetse's reproductive biology.” Tsetse flies, prevalent in much of sub-Saharan Africa, are known for vectoring human African trypanosomiasis, also known as sleeping sickness.
A native of Poughkeepsie, N.Y., Geoffrey received his bachelor's degree in entomology from the University of Massachusetts, Amherst, in 1994 and his doctorate in genetics from Michigan State University, East Lansing, in 2004.
A career in science came naturally. “My parents are both somewhat scientifically inclined, so I may have taken after them,” he says. “My father has a doctorate in metallurgy from Columbia University and led a long successful career at IBM. My mom was a full-time mom, but has a background in microbiology with a master's degree from Yale.”
“I decided to develop my career in science and went to work in Dr. Alexander Raikhel's lab at Michigan State University as a graduate student. I was always drawn to understanding the molecular mechanisms underlying the extreme biology of insects and Dr. Raikhel's lab provided that opportunity. There I focused on the molecular biology of egg development in mosquitoes.”
In research on mosquitoes, Attardo demonstrated that mosquitoes require nutritional cues to begin egg development. “Egg development had been known to be regulated by a steroid hormone called 20-hydroxyecdysone,” Attardo explained. “However, treatment of mosquitoes with this hormone along did not activate egg development. My research showed that when female mosquitoes take blood, the protein in the blood is broken down into amino acids which in combination with the hormone activate egg development. Either amino acids or the hormone along were not capable of activating this process, but when they are combined it unlocks a massive physiological change which causes the production of yolk proteins and activation of egg development.”
After receiving his doctorate, Attardo joined the Yale lab of Serap Aksoy to work on tsetse flies. “In terms of fascinating physiological adaptations, the tsetse fly is one of the champions of the insect world!” Attardo says. “In addition to being vectors of a deadly disease, Trypanosomiasis, these flies have undergone amazing alterations to their physiology relative to other insects. Some examples of this are their ability feed exclusively on blood, their obligate relationship with a bacterial symbiont, the fact that they lactate and that they give birth to fully developed larval offspring. The opportunity to study the adaptations these flies have made is like opening a toy chest for an insect physiologist. My work in tsetse has focused on the molecular biology underlying the adaptations associated with the development of lactation, symbiosis, male and female mating interactions/physiology and nutrient metabolism and mobilization.”
His tsetse research also includes identifying the tsetse milk proteins and the genes that code for them. Said Attardo: “They are really interesting as they are functionally very similar to milk proteins in mammals!”
In newly published research (June) in the Proceedings of the Royal Society B, he and his colleagues examined the relationship between the fly and its obligate symbiotic bacteria called Wigglesworthia. “Tsetse flies without their symbionts are unable to reproduce and abort their larvae before the complete development,” he says. “We showed that the bacteria supplements the flies diet with B vitamins and that the fly appears to scavenge nucleotides (the component molecules of DNA and RNA) made by the bacteria. The B-vitamins made by the bacteria enable the fly to metabolize nucleotides, sugars, amino acids and produce chemicals essential for its overall metabolism.”
Attardo traces his interest in insects and macro photography to his childhood. “I had always been fascinated with insects, but my earliest memory was feeding insects to a beautiful black and yellow garden spider (Argiope aurantia) that had set up her web in front of the bay window of our house. I was especially interested in spiders. Another early memory was being sick in bed with the croup and reading--and rereading multiple times--through a picture book I had on spiders that had amazing macro photos. I found jumping spiders particularly fascinating. From that point on I had been fascinated with seeing insects up close, but it was not until I was able to afford a good digital camera and the appropriate lenses that I was able to get into insect photography.”
Attardo's first professional camera was a Canon that he received in the mid-1990s.
His first digital? A Canon Rebel XT. He now uses a Canon EOS 5D Mark IV with macro lenses, the MPE-65mm and the 100mm.
“I love macro photography because it reveals the amazing details that are present in things that many people take for granted or for mundane,” Attardo says. “Insects especially benefit from macro treatment as I find that most people have no idea about the type of amazing creatures they have living in their yard or even in their house. I'm often asked if my photos were taken in South America, Africa or Asia as the insects appear to be so exotic, however, they are often surprised --and sometimes dismayed--to find out that most of my photos are taken locally.”
The many shapes, sizes and designs of insects fascinate him. “I am a bit of a science fiction geek and I find insects to be almost alien in how different they are from vertebrates. It is like traveling to another planet when you start to magnify the world. I am endlessly fascinated with all the different strategies and adaptations they have developed to survive/thrive in places where many animals couldn't. I think by taking photos of them it allows me to open a window and share my fascination with people who don't normally give much consideration to insects and treat them just as bugs or an annoyance.”
“As a scientist, I have taken my fascination with the magnifying things to the extreme in that my work tends to focus on the molecular biology underlying the physiology of insect adaptations. The molecular adaptations are just as amazing as the morphological ones. However, they are even harder to visualize and explain to lay people. I enjoy illustration and artwork as well, so when it is not possible to take a picture of something I am working on, I try to create a visual representation of it.”
“I also really enjoy digital illustration and have recently gotten into 3D modeling. My first model is a tsetse fly for which I was able to use my macro photos to texture. See (https://sketchfab.com/models/263750e5a9c54c56a77d63ac06f2f317
He and his wife, Meg Gurley and their son, Douglas, 13, are settling into their home in Davis. "Meg is a full-time mom currently," he says, "and a Master Gardener. We have a symbiotic relationship as she grows the plants that attract the insects I like to photograph. Douglas and I are both into computers and computer gaming together."
Future lab plans? Attardo said three undergraduates will join his lab in the fall, helping him to “get the lab set up and running.” He hopes to hire a lab manager, a postdoc and “a couple of graduate students.”
A few of the projects he is excited to pursue:
- Study of lipid metabolism during tsetse pregnancy and the role that symbiotic bacteria play in this process.
- Understanding the molecular mechanisms that regulate the expression of genes coding for milk proteins during the lactation cycle.
- Understanding the physiology behind mating effects on female tsetse flies and the role of male seminal secretions on female fertility.
- Comparative genomic analysis of different tsetse species to identify factors associated with vectorial capacity.
- Understanding the nutritional and metabolic impact of trypanosome infection on female tsetse flies and their reproduction.
- Development of new non-invasive detection techniques to measure changing physiological states and determine trypanosome infection in flies using hyperspectral imaging.
Geoffrey Attardo invites “anyone who is interested in meeting me and talking science, photography or anything else to stop by the lab and visit! My door is always open--unless I have a grant due!”
He can be reached at firstname.lastname@example.org.