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.

Homepage：https://www.ecology.kyoto-u.ac.jp/~tsato/index-e.html

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.

Homepage：https://sites.google.com/site/nishihdlab/english-site

A01-K1-1

Molecular and neural mechanisms that plants manipulate insect behavior

KIYA Taketoshi (Kanazawa University)

It is believed that insects visit flowers on their own will, where plants depend on insects for pollination by providing nectar and odors that the insects prefer. These interaction sometimes caused co-evolve among them. We recently found the possibility that insects' flower-visiting behavior is manipulated by plants, which is contrary to the common notion. In this study, we will examine the hypothesis that plant pollen functions as an endobiont and manipulates the insect's behavior by acting on its brain function, and elucidate the molecular and neural mechanisms.

Homepage：https://researchmap.jp/read0123419?lang=en

A01-K1-2

Elucidation of the mechanism of host-aggressive behavior induced by rabies virus infection

MASATANI Tatsunori (Gifu University)

Rabies virus multiplies in the host's central nervous system, causing a significant change in the host's emotional state and inducing aggressive behavior such as biting the animal in front of him. At the same time, the virus is secreted from the salivary glands and transmitted to other individuals via bites. This study aims to elucidate the mechanism by which viruses manipulate the host's emotional state and physiology by inducing neural abnormalities. Furthermore, we will attempt to identify “effector proteins,” which are factors on the viral side.

A01-K1-3

Aggression in Males Controlled by Endobiont

HORI  Aki（Kanazawa University）

Aggressive behavior between males is an instinctive trait widely observed across the animal kingdom. It plays crucial roles in ensuring species survival and the formation of social structures. We previously found that lactic acid bacteria, symbiotic microbes in Drosophila melanogaster (fruit flies), can suppress male aggressive behavior. In this research, we aim to elucidate the molecular mechanisms by which these bacteria modulate aggression in the host.

To this end, we will conduct genetic analyses using mutant strains of lactic acid bacteria to identify the effector molecules responsible for the suppression of aggression. Furthermore, we will investigate the neural substrates in the host that are targeted and manipulated by these bacteria. This study will contribute to our understanding of how symbiotic microbes can influence the host central nervous system and induce extended phenotypes.

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.

Homepage：https://sites.google.com/site/kageyama000/

A02-5

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

HARUMOTO Toshiyuki（University of Tsukuba）

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.

Homepage：https://researchmap.jp/toshiyukiharumoto?lang=en

A02-K1-5

Comparative analysis of male-to-female sex reversal mechanisms in host decapod crustaceans by parasitic barnacles

TOYOTA Kenji（Hiroshima University） 

Rhizocephalans are parasitic barnacles specialized in infecting crustacean hosts. They exploit their hosts, such as crabs and hermit crabs, by extracting nutrients and suppressing the host’s reproductive capacity (parasitic castration). In male hosts, they further induce morphological and behavioral feminization (parasitic feminization). Focusing on this remarkable feminization phenomenon, our research employs rhizocephalans that commonly parasitize coastal species like the intertidal crabs and various hermit crabs as model systems. Through a combination of multi-omics approaches and physiological experiments, we aim to elucidate the molecular mechanisms underlying rhizocephalan-induced feminization in their hosts.

Homepage：https://sites.google.com/site/toyotadaphnia/home

A02-K1-6

Host manipulation through higher-order RNA structures mediated by symbiotic bacteria

OTE Manabu (The Jikei University School of Medicine)

Wolbachia, a widespread endosymbiont in insects, is known to confer resistance against viral pathogens. In the mosquito vector Aedes aegypti, this symbiotic relationship effectively suppresses the transmission of dengue virus and other arboviruses. The goal of this research is to elucidate the molecular mechanisms underpinning this Wolbachia-mediated antiviral protection. Our hypothesis is that host- and symbiont-derived factors modify viral RNA molecules, thereby altering viral phenotypes and inhibiting replication. We will employ a Drosophila-insect virus model to establish a mechanistic framework, which will then be validated in the context of Aedes and its pathogenic viruses to uncover fundamental, conserved principles of host-symbiont-virus 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.

Homepage：https://staff.aist.go.jp/m-kutsukake/index_en.html

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. 

A03-K1-7

Mechanistic insights into nematode-induced modulation of plant morphology and growth-related physiology

SAWA Shinichiro（Kumamoto University）

Plant-parasitic nematodes invade host roots and establish a parasitic relationship.

We are investigating the molecular mechanisms underlying nematode-induced extended phenotypes in plants, focusing on how root-knot nematodes that penetrate the roots of Arabidopsis thaliana induce novel root gall formation, manipulate plant physiological processes during gall development, and subsequently alter flowering time.

To date, we have isolated five candidate CLE effector peptides from the sweet potato root-knot nematode (Meloidogyne incognita), and identified multiple homologous plant-derived CLE peptides. Given that cle mutants exhibit early flowering and CLE overexpression lines show delayed flowering, our first research goal is to elucidate how nematode infection regulates flowering through these peptides, thereby uncovering the molecular basis of the nematode-induced extended phenotype.

On the other hand, we discovered that applying nematode lysate to Arabidopsis roots can also induce root gall formation. In parallel, recent work by Hirano and colleagues at Kyoto Prefectural University has begun to uncover the molecular basis of gall formation induced by the aphid Schlechtendalia chinensis on Chinese sumac.

Therefore, as a second research goal, we aim to clarify the similarities and differences in gall formation mechanisms across three systems:

(A) gall formation induced by nematode infection,

(B) gall formation induced by nematode lysate (our novel finding), and

(C) insect gall formation by S. chinensis.

By comparing RNA-seq data across these systems, we seek to reveal commonalities and divergences in the molecular basis of gall formation.

Ultimately, this research will provide insights into the molecular mechanisms by which phylogenetically distant endoparasites induce extended host phenotypes, and how specific parasite–host combinations have co-evolved.

Homepage：https://www.sci.kumamoto-u.ac.jp/~sawa/EN/

A03-K1-8

Uncovering the Molecular Basis of Gall-Inducing Factors in Insect–Bacterium Symbioses

TSUCHIDA Tsutomu (University of Toyama)

Gall formation by insects is a phenomenon that has attracted interest across various fields of biology. However, due to the difficulty of reproducing and manipulating this process under laboratory conditions, its underlying mechanisms remain largely unexplored. We have established a stable laboratory system for studying the gall-forming Smicronyx madaranus, an insect with a uniquely intriguing ecology: it parasitizes the parasitic plant Cuscuta campestris (dodder) and induces gall formation.

Through our investigations, we have discovered that all individuals of this beetle species harbor endosymbiotic bacteria belonging to the genus Sodalis, and our findings suggest that these bacteria play a crucial role in gall induction.

In this project, we aim to identify the gall-inducing factors produced by this beetle, focusing on a highly nested symbiotic system that comprises the host plant, parasitic plant, insect, and symbiotic bacteria.

Homepage：http://www3.u-toyama.ac.jp/symbiont/english.html

A03-K1-10

Molecular mechanism of bacterial inhibition of plant flower development

IWABUCHI Nozomu (The University of Tokyo)

Plant pathogens induce diverse symptoms that reduce crop yield and quality, highlighting the importance of elucidating the molecular mechanisms by which pathogens manipulate host development. While many pathogen-induced phenotypic alterations have been attributed to the disruption of plant hormone pathways—such as those involving gibberellin, auxin, and cytokinin—the contributions of pathogen-derived effectors to developmental reprogramming remain poorly understood. Among plant organs, flowers are essential reproductive structures in angiosperms, facilitating sexual reproduction, promoting genetic diversity, and contributing to defense against pathogen invasion. Phytoplasmas, obligate parasitic bacteria transmitted by phloem-feeding insects, cause striking disruptions to floral development. These pathogens suppress flower formation and induce a developmental reversion from reproductive to vegetative growth, resulting in persistent vegetative traits and the loss of flowering capacity. Despite the dramatic nature of these alterations, the molecular basis underlying phytoplasma-induced suppression of floral development remains largely unknown. This study aims to identify the effector proteins responsible for redirecting plant developmental programs and to elucidate the regulatory pathways they target. Furthermore, the biological significance of pathogen-mediated reproductive inhibition will be investigated within an evolutionary framework. By integrating developmental biology, molecular plant pathology, and evolutionary ecology, this research contributes to the emerging field of co-evolutionary molecular developmental ecology. It also advances the concept of the extended phenotype by illustrating how pathogen effectors can reshape host morphology to serve parasitic interests. These insights will deepen the understanding of how pathogens reprogram host developmental systems and reveal evolutionary strategies that underlie host 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.

A05-K1-12

Molecular mechanisms underlying plant-fungus interactions in symbiosis through peptide hormone mimicry

FURUMIZU Chihiro (Shimane University)

More than 80% of terrestrial plants establish symbiosis with arbuscular mycorrhizal (AM) fungi, which facilitate the uptake of inorganic salts from the soil. Short peptides similar to the plant peptide hormone CLE (AM-CLEs) have been reported as potential effectors secreted by AM fungi during this process. However, the role of AM-CLE remains unclear. In this study, we aim to clarify the origin of AM-CLE and its function in symbiotic relationships with plants. The phylogenetic distribution of CLE-like peptides in fungi will be explored, and plant receptor systems for AM-CLE will be elucidated using two liverwort species (photo: Marchantia polymorpha). The long-term goal of this study is to contribute to our understanding of the molecular basis for the evolution of molecules that mimic host bioactive molecules as effectors in cross-species interactions.

Homepage：https://www.ipc.shimane-u.ac.jp/evobio/