Evolution of the innate immune system
The mushroom-feeding species Drosophila innubila
“Now here, you see, it takes all the running you can do, to keep in the same place,” - Lewis Carroll
A robust immune system is essential to defend yourself from "non-self" invaders. However the type of invader varies from location to location, and through time. This requires the host immune defence to adapt to novel threats from unique parasites and pathogens. Insects and arthropods are incredibly important disease vectors. It is no exaggeration to say that all human beings are at risk of contracting disease from insects: The World Health Organization suggests that dengue-vector mosquitoes alone pose a risk to ~3.9 billion people globally. Insects are also major vectors of plant diseases. These diseases can be caused by a variety of parasites and pathogens, including viruses, bacteria, fungi, trypanosomes, nematodes, and more, all via insect intermediates.
Drosophila melanogaster has been an incredible genetic model for understanding how the insect immune response signals the threat of infection and responds with the production of immune effectors. However D. melanogaster is a unique species whose immune repertoire diverges from other insects in terms of gene copy number and specificity of immune signalling. My research seeks to inform on how immune processes in D. melanogaster translate in a more general fashion to other insects. For this, I use other Drosophila species with unique ecologies that drastically change the infectious pressures faced by the host. By incorporating the wealth of diversity in the genus Drosophila, I study how different parasites and pathogens interact with the Drosophila immune response, and in the future hope to use host-parasite interactions beyond those available in D. melanogaster infection models to improve the application of Drosophila research in managing infectious diseases.
A robust immune system is essential to defend yourself from "non-self" invaders. However the type of invader varies from location to location, and through time. This requires the host immune defence to adapt to novel threats from unique parasites and pathogens. Insects and arthropods are incredibly important disease vectors. It is no exaggeration to say that all human beings are at risk of contracting disease from insects: The World Health Organization suggests that dengue-vector mosquitoes alone pose a risk to ~3.9 billion people globally. Insects are also major vectors of plant diseases. These diseases can be caused by a variety of parasites and pathogens, including viruses, bacteria, fungi, trypanosomes, nematodes, and more, all via insect intermediates.
Drosophila melanogaster has been an incredible genetic model for understanding how the insect immune response signals the threat of infection and responds with the production of immune effectors. However D. melanogaster is a unique species whose immune repertoire diverges from other insects in terms of gene copy number and specificity of immune signalling. My research seeks to inform on how immune processes in D. melanogaster translate in a more general fashion to other insects. For this, I use other Drosophila species with unique ecologies that drastically change the infectious pressures faced by the host. By incorporating the wealth of diversity in the genus Drosophila, I study how different parasites and pathogens interact with the Drosophila immune response, and in the future hope to use host-parasite interactions beyond those available in D. melanogaster infection models to improve the application of Drosophila research in managing infectious diseases.
Antimicrobial peptides: natural antibiotics of the innate immune system
A 3D model of the AMP "Drosomycin"
"We shape our buildings; thereafter they shape us." - Winston Churchill
Antimicrobial peptides (AMPs) are host-encoded antibiotics that combat invading microorganisms. These peptides are produced at pretty much any surface that comes in contact with microbes in the environment: in the gut, genitalia, skin, and at mucosal membranes in the lungs, eyes etc... My thesis work in Bruno Lemaitre's lab has shown that the constant secretion of these peptides is a key determinant in the composition of the microbiome, and in many host-microbe interactions. Their production is regulated by the "innate immune system," a rapid front-line defence against infection before the involvement of antigens and antibodies, i.e. before the "adaptive immune system." In vertebrates, AMPs are also known to regulate inflammatory signalling and other infectious processes. Dysregulation of AMPs is implicated in a number of diseases including susceptibility to chronic infections (e.g. atopic dermatitis), autoimmune disorders (e.g. inflammatory bowel disease), lung infections (e.g. in parkinson's disease patients), and neurodegenerative disorders (e.g. alzheimer's disease). Each of these processes can be impacted by intimate associations between hosts and their microbes.
AMPs must strike a fine balance: being toxic enough to kill invading microbes but not so toxic as to disrupt host cells or beneficial microbes of the gut microbiome. I use Drosophila as a model to understand how variation in AMP sequence can impact function, and how sequence evolution responds to infectious pressures. I've found that AMPs can have remarkably specific interactions with microbes, wherein a single AMP gene can dictate success or failure in fighting off infection. Over the course of fly evolution, species with highly-specialized ecologies also show microbe-specific patterns of antimicrobial peptide evolution. It's no exaggeration to say that this model in fruit flies teaches us that our resident microbes shape the immune repertoire present in our genomes. Through our ecology and behaviours, we expose ourselves to a common set of microbes over our lifetimes, and it turns out those microbes have also put pressure on our genomes to be prepared. We shape our buildings, thereafter they shape us. This research brings a number of interesting questions to the fore, regarding chronic infectious or dysbiosis syndromes such as inflammatory bowel, atopic dermatitis, chronic lung infections, etc... Could such chronic infectious diseases be treated if we could identify specific AMPs/effectors that are evolutionarily adapted to control them?
Antimicrobial peptides (AMPs) are host-encoded antibiotics that combat invading microorganisms. These peptides are produced at pretty much any surface that comes in contact with microbes in the environment: in the gut, genitalia, skin, and at mucosal membranes in the lungs, eyes etc... My thesis work in Bruno Lemaitre's lab has shown that the constant secretion of these peptides is a key determinant in the composition of the microbiome, and in many host-microbe interactions. Their production is regulated by the "innate immune system," a rapid front-line defence against infection before the involvement of antigens and antibodies, i.e. before the "adaptive immune system." In vertebrates, AMPs are also known to regulate inflammatory signalling and other infectious processes. Dysregulation of AMPs is implicated in a number of diseases including susceptibility to chronic infections (e.g. atopic dermatitis), autoimmune disorders (e.g. inflammatory bowel disease), lung infections (e.g. in parkinson's disease patients), and neurodegenerative disorders (e.g. alzheimer's disease). Each of these processes can be impacted by intimate associations between hosts and their microbes.
AMPs must strike a fine balance: being toxic enough to kill invading microbes but not so toxic as to disrupt host cells or beneficial microbes of the gut microbiome. I use Drosophila as a model to understand how variation in AMP sequence can impact function, and how sequence evolution responds to infectious pressures. I've found that AMPs can have remarkably specific interactions with microbes, wherein a single AMP gene can dictate success or failure in fighting off infection. Over the course of fly evolution, species with highly-specialized ecologies also show microbe-specific patterns of antimicrobial peptide evolution. It's no exaggeration to say that this model in fruit flies teaches us that our resident microbes shape the immune repertoire present in our genomes. Through our ecology and behaviours, we expose ourselves to a common set of microbes over our lifetimes, and it turns out those microbes have also put pressure on our genomes to be prepared. We shape our buildings, thereafter they shape us. This research brings a number of interesting questions to the fore, regarding chronic infectious or dysbiosis syndromes such as inflammatory bowel, atopic dermatitis, chronic lung infections, etc... Could such chronic infectious diseases be treated if we could identify specific AMPs/effectors that are evolutionarily adapted to control them?
