A01-1

Molecular mechanisms underlying baculovirus-induced host behavior manipulation

KATSUMA Susumu（The University of Tokyo）

Pathogens sometimes alter the behavior of their hosts so that progeny transmission is maximized. One of the earliest documented examples of such behavior modification is Wipfelkrankheit, a baculovirus-induced disease that causes caterpillars to migrate to the upper foliage of food plants where they die. We and other groups have identified two baculovirus genes, ptp (protein tyrosin phosphatase) and egt (ecdysteroid UDP-glucosyltransferase), as the key factors for baculovirus-induced abnormal behavior during the late stage of infection (Hoover et al., 2011, Science; Kamita et al., 2005, PNAS; Katsuma et al., 2012, PLoS Pathog.). Interestingly, both of them are likely captured from ancestral lepidopteran insects by horizontal gene transfer, suggesting that the modern baculovirus uses captured host genes for manipulation of host behavior. On the other hand, host genes involved in baculoviral behavior manipulation remain largely unknown. In this study, we aim to identify the viral effectors and host signal cascades involved in baculovirus-induced host behavior manipulation, and explore the strategy of how baculoviruses have evolved to hijack host behavior.

A01-2

Molecular mechanisms of host behaviour manipulation by parasites

SATO Takuya（Kyoto University）

A fascinating example of the extended phenotypes is observed in nematomorphs that manipulate their terrestrial hosts (e.g., mantises and orthopterans) to enter water. This behavioral manipulation allows the parasites to return to aquatic habitats where they reproduce as adults. Once inside their hosts, the worms induce remarkable behavioral changes, including increased activity levels, which likely increase the likelihood of encountering water, and enhanced positive phototaxis to horizontally polarized light reflected from water surfaces, which ultimately triggers the host's water-entry behavior. In addition, we have recently discovered numerous possible host-derived genes in nematomorphs, and these genes were often up-regulated during host manipulation. However, the precise molecular mechanisms underlying behavioral manipulation remain largely unknown.

In this study, we aim to (1) identify candidate genes and effector molecules involved in behavioral manipulation, (2) understand the mechanisms by which parasites interfere with host signaling cascades, and (3) investigate whether and how horizontal gene transfer underlies the molecular mechanisms of host manipulation. Through these efforts, we seek to thoroughly elucidate the molecular mechanisms and their genome evolution by which nematomorphs achieve the terrifying manipulation of causing their terrestrial hosts to jump into water.

A01-3

Study of Molecular Mechanisms of Host Behavior Manipulation by Toxoplasma gondii

NISHIKAWA Yoshifumi（Obihiro University of Agriculture and Veterinary Medicine)

Toxoplasma gondii is an intracellular protozoan parasite that can infect mammals and birds as intermediate hosts and cats as definitive hosts. T. gondii forms cysts in the brain and muscle of intermediate hosts at chronic infection stage. Recent studies have reported that chronic infection with T. gondii can alter behavior in rodents and increase the risk of developing psychiatric and neurological disorders in humans. Therefore, the various effects on neurological functions in animals including humans might contribute on the survival strategy of T. gondii. Our study using mouse models demonstrated the development of depression-like symptoms involving the host immune response during the acute phase of infection and impaired memory performance due to modulation of neurotransmitters in the central nervous system during the chronic phase of infection. These analyses suggest that the central nervous system of the host animal will be affected by effector molecules derived from T. gondii, but the molecules have not been identified. This study will elucidate the molecular basis for the manipulation of host behavior by Toxoplasma-derived effector molecules.

A02-4

Sex Manipulation by Intracellular Symbionts: Mechanisms, Diversity, and Evolution

KAGEYAMA Daisuke（NARO）

Many insects harbor a variety of symbionts within their cells that are maternally transmitted across generations. These symbionts, which are not passed from father to offspring, can manipulate the host's reproductive systems, sometimes resulting in offspring exclusively composed of females. While numerous intracellular symbionts, including bacteria and viruses, are known to influence insect sex, the underlying molecular mechanisms have only been partially elucidated in a few systems and appear surprisingly diverse. For instance, some symbionts manipulate host sex-determining mechanisms, while others employ entirely different strategies. Notably, we recently demonstrated that the manipulation of sex-determining mechanisms can also be studied in cultured cells.

This project aims to explore the mechanistic and evolutionary commonalities and differences in sex manipulation across diverse host-symbiont systems. Specifically, we seek to (1) analyze symbiont-induced host manipulations at both the phenotypic and molecular levels using a variety of insects, including butterflies, moths, flies, lacewings, and insect cell cultures, and (2) identify the genes responsible for host manipulation within the genomes of symbiotic bacteria and viruses. Additionally, we aim to uncover how and why such seemingly diverse mechanisms evolved in various insect species and to assess their broader implications for the evolution of eukaryotic life.

A02-5

Sexual manipulation by insect symbionts - the diverse molecular basis of the symbiosis

HARUMOTO Toshiyuki（Kyoto University）

It is estimated that approximately half of all insect species on Earth harbor symbiotic microorganisms within their bodies. These symbiotic microorganisms play a crucial role in supporting the survival and prosperity of insects, primarily by providing essential nutrients to their hosts and conferring resistance or tolerance against natural enemies. However, some symbiotic microorganisms exhibit selfish behavior, attempting to expand their infection by manipulating the reproduction of their host insects. This reproductive manipulation can be viewed as an extended phenotype that has evolved through the intricate interactions between insects and microorganisms. 

Our research project aims to unravel the underlying molecular mechanisms of reproductive manipulation across a wide variety of insect-microbe symbiotic relationships. Depending on the specific combination of insects and symbiotic microorganisms under study, we employ sophisticated genetic tools in model insects or apply cutting-edge genome editing and genetic modification technologies in non-model insects. By elucidating both the diversity and commonality in these molecular mechanisms, we aim to shed light on the evolutionary strategies and adaptive processes that shape insect-microbe interactions.

A03-6

Elucidation of mechanisms underlying plant morphological manipulation and floral induction by insects

KUTSUKAKE Mayako（AIST）

Galls, also known as plant galls, are uniquely shaped structures formed on plants by insects and other organisms. They develop when insects physically or chemically stimulate specific parts of plants, inducing hypertrophy or hyperplasia of cells in young plant tissues and the development of conspicuous plant morphologies. Interestingly, the gall morphology is attributable to insect species that induce it, rather than to plant species on which it forms. Moreover, the gall morphology is consistent and reproducible within insect species, suggesting that the gall

formation is precisely controlled by genetic factors of the inducer insects.

Therefore, the morphological traits of the galls are often regarded as the “extended phenotypes” of the inducer insects.

In this study, to gain insight into the molecular mechanisms underlying gall formation and function, we focus on Ceratovacuna nekoashi, which forms banana-shaped galls on the tree Styrax japonicus. In this system, a unique phenomenon called “late flowers” is observed, in which abnormal flowers bloom from failed galls. Using this system, we aim to elucidate the molecular mechanisms of gall formation in the light of flower formation system of the host plant, from the perspectives of both insects and plants.

A03-7

Molecular mechanisms of plant morphological manipulation by insects using model plant experimental systems

HIRANO Tomoko（Kyoto Prefectural University） 

Some insects manipulate plants to produce an 'insect gall', where they spend a safe larval period before becoming adults. The insect gall is not a simple cluster of cells, but a highly ordered organ adapted to insects, consisting of a nutrient-rich tissue in an inner layer, vascular bundles to transport water and nutrients, and hard tissue to protect against external enemies in an outer layer. Gall formation has been a mysterious phenomenon for many centuries and its molecular mechanism is still largely unknown. 

It has been well known that "the mechanism of gall formation cannot be generalized" because different insects, such as aphids, moths, flies, bees and weevils, form different insect galls on specific host plants. On the other hand, the gall-inducing insects and host plants have not been modelled.

We found the common features of 'insect gall' by comparing gene expression analyses of different types of gall and concluded that insect gall formation is caused by the partial expression of floral organ genes and fruit genes. 

We found that these genes are induced by the reaction between insect-secreted CAP peptides and the plant-side receptor CAPR to successfully reconstruct an artificial insect gall. 

In this study, we aim to comprehensively elucidate the molecular mechanism of 'CAP-CAPR signaling', which is at the core of plant morphological manipulation. 

A04-8

Molecular basis for the skilful manipulation of development by venom of the domesticated parasitic bee

NIWA Ryusuke（University of Tsukuba）

Parasitoid wasps, belonging to the family Hymenoptera, deprive their insect and spider hosts of nutrition. These wasps represent approximately 20% of the one million insect species on Earth, making them one of the planet’s most successful animal groups.

Certain types of parasitoid wasps, known as “koinobiont” endoparasitoid wasps, inject their hosts with hundreds of different venom components simultaneously, suppressing the involution of specific host tissues and immune responses before ultimately killing the host after a certain period. This process results in what is known as a "koinobiont" effect. To unravel this sophisticated manipulation of the host's developmental and physiological processes, it is crucial to characterize the nature of koinobiont endoparasitoid wasp venoms and elucidate the molecular mechanisms underlying their effects on the host. Additionally, each koinobiont endoparasitoid wasp species exhibits unique host specificity, a feature that has long fascinated researchers from ecological and evolutionary perspectives. However, the mechanisms by which koinobiont endoparasitoid wasps distinguish between suitable and unsuitable hosts, particularly in relation to venom diversity and its specific actions, remain largely unexplored.

In this project, we focus primarily on koinobiont endoparasitoid wasps of the genus Asobara, which parasitize Drosophila fruit flies. We aim to uncover the molecular basis by which these venoms manipulate host development and physiology.

A05-9

Elucidating the molecular basis of host phenotypic transformation by symbiotic bacteria

FUKATSU Takema（AIST）

Thus far, the “extended phenotypes”, which emerge as remarkable phenotypic modifications through proximate inter-organismal interactions, have been discussed mostly in the context of “parasitic” relationships. On the other hand, in “mutualistic” relationships, such phenotypic modifications must have been manifested through cooperative evolution rather than through competitive/antagonistic evolution. Here, we will elucidate the molecular mechanisms underpinning host’s phenotypic alterations induced by symbiotic bacteria using stinkbug’s obligatory gut symbiotic system. Specifically, we will elucidate “the mechanisms of symbiotic body color transformation, in which the cryptic green body color of the insect is formed by host-symbiont interactions” and “the mechanisms of symbiotic behavioral modification, in which the host insect's behavior shaped for vertical transmission of the essential symbiont is controlled by host-symbiont interactions. By comparing the molecular mechanisms of “competitive phenotypic manipulations” in parasitic relationships and “cooperative phenotypic alterations” in mutualistic relationships, we aim to understand the nature of phenotypic co-evolution encompassing parasitism through commensalism to mutualism in an integrated perspective.