Research grants
PIs:
Salva Herrero and Cristina Crava
FUNDING AGENCY:
Agencia Española de Investigación
Duration: 01/09/2025-31/08/2028
Summary:
Herbivorous pests manipulate plant defenses to optimize their feeding success. Plants detect herbivore feeding through damage-associated molecular patterns (DAMPs) and herbivore-associated molecular patterns (HAMPs), triggering jasmonate (JA)-mediated defenses that produce toxic compounds and attract natural enemies. Recent discoveries highlight the role of insect-derived lipases in eliciting plant defenses by hydrolyzing plant lipids, which serve as precursors for defensive metabolites. Additionally, herbivores secrete effectors, such as REPAT proteins, to suppress plant defenses by interfering with JA signaling. These herbivore-derived modulators (HeDeM) are highly plastic, influenced by the insects physiological state and even by infections with entomopathogens like baculoviruses. For instance, viral infections alter HeDeM profiles, reducing lipase activity while increasing REPAT expression, potentially suppressing plant defenses to enhance viral spread and herbivore fitness. Furthermore, Microbe-induced resistance (MIR) modulates plant-insect interactions by priming plants for stronger and faster defense responses. These changes affect HeDeM secretion and plant herbivore dynamics, potentially influencing insect adaptation and ecological interactions. Building on expertise developed in previous projects, we aim to explore the molecular mechanisms underlying HeDeM plasticity, the role of viral infections in modulating plant defenses, and the ecological consequences of MIR-mediated changes in herbivore traits. This research will provide new insights into the complex multitrophic interactions between plants, herbivores, microbes, and their associated pathogens.
PIs:
Leopoldo Palma Dovis
FUNDING AGENCY:
IIS La Fe-University of Valencia
Duration: 01/01/2025 – 31/08/2026
Summary:
This project aims to develop a local collection of Photorhabdus and Xenorhabdus strains isolated from soils in the province of Valencia, Spain, and to evaluate their potential to produce novel antimicrobial compounds. These bacteria, natural symbionts of entomopathogenic nematodes, synthesize a wide diversity of insecticidal proteins and secondary metabolites with documented antibacterial and antifungal activities. Given the alarming global rise of antimicrobial resistance, these bioactive compounds represent a highly promising and underexplored alternative to existing antibiotics. A key innovative aspect lies in the exploration of novel strains from a geographically uncharacterized niche, increasing the likelihood of discovering previously unknown antimicrobial metabolites to which pathogens may have no innate resistance. The initiative will establish a collaborative research platform between the University of Valencia and the IIS La Fe Institute, integrating basic microbiology with clinical expertise.
PIs:
Leopoldo Palma Dovis
FUNDING AGENCY:
Spanish Ministry of Science, Innovation and Universities
Duration: 01/01/2025 – 31/12/2029
Summary:
The microbial insecticide market was valued at approximately USD 400 million in 2010 and is expected to reach USD 4.6 billion by 2025, as agriculture transitions away from chemical pesticides toward biological control methods. Biological control of pests and crop diseases is essential for environmentally friendly agriculture, as both significantly reduce yields worldwide. Currently, microbial insecticides are dominated by the Gram-positive entomopathogenic bacterium Bacillus thuringiensis (Bt); however, several pest species have evolved resistance to Bt sprays and transgenic crops (e.g., Plutella xylostella). To address this challenge, this research proposes to harness the exceptional biotechnological potential of Xenorhabdus and Photorhabdus bacteria. These symbionts of insect-parasitic nematodes produce a remarkable diversity of insecticidal proteins and secondary metabolites, many of which remain uncharacterized. This project will systematically explore these novel bioactive molecules to provide a foundation for innovative pest management strategies and strengthen global efforts toward sustainable agriculture.
PIs:
Laila Gasmi
FUNDING AGENCY:
Agencia Española de Investigación
Duration: 01/09/2025-31/08/2028
Summary:
Exotic insects, often harmless in their native habitats due to natural enemies, become major agricultural, environmental, and economic challenges in new environments. Mealybugs are particularly problematic due to small size, stealthy behavior, and ability to cause significant crop damage. This exacerbates the challenge of meeting global food demands while protecting biodiversity and economic productivity. In Spain, the mealybug Delottococcus aberiae, detected in Valencia in 2009, has become a highly destructive citrus pest, causing up to 80% yield losses in heavily infested orchards. With no native enemies to control the pest, Spanish government authorized the import of its natural enemy from South Africa, and since 2019, the parasitoid Anagyrus aberiae has been released in a classical biological control strategy (CBC). CBC strategies often face challenges as they can be resource-intensive, require long-term monitoring, and may disrupt ecosystems and biodiversity. Public skepticism and regulatory hurdles further complicate implementation. Parasitoids, key to biological control, use virulence factors like symbiotic viruses to overcome host defenses. Symbionts can sometimes invade new hosts; thus, symbiotic viruses might transmit between native and introduced parasitoids if they share genetic and biological similarities. Anagyrus aberiae is closely related to the naturalized Anagyrus vladimiri controlling the native citrus pest Planococcus citri. Despite no cross-parasitism has been observed, both parasitoids can recognize both mealybugs as potential hosts. It might be particularly interesting to explore the potential role of viruses in shaping host-parasitoid specificity. VIRPAPEST proposes to enhance parasitism success of A. aberiae by characterizing the implication of a symbiotic virus specific to this parasitoid. This knowledge will be used to manipulate symbiotic viruses in A. vladimiri attempting to enhance its host range to D. aberiae and to improve its fitness against secondary parasitoids. This project aims to make use of viral symbionts to enhance native natural enemies’ ability to control invasive species. This will foster sustainable agriculture and help overcome economical and legal limitations imposed by importation of natural enemies.
PIs:
Laila Gasmi
FUNDING AGENCY:
Spanish Ministry of Science, Innovation and Universities
Duration: 01/03/2024-28/02/2029
Summary:
Global food security is a major worldwide concern that requires an increase in production while protecting the environment. In this regard, research efforts to develop eco-friendly pest management strategies are being carried out worldwide. Despite their biodiversity richness, a limited number of entomopathogens and natural enemies are currently part of integrated pest management (IPM) strategies. In addition, insects are in dynamic interactions with components of their ecosystems. Variable interactions between insects, their plant hosts, microorganisms and natural enemies might exert variable selection pressures which would differently affect the extent of damage caused by insects and efficiency of the applied biological control agent. Therefore, considering mixed infections, the complex multitrophic interactions of the insect in its ecosystem and what drives the evolution of the insect immune mechanisms is primordial to design optimum pest control strategies that involve pathogens such as insect viruses. Combining knowledge from different fields (e.g., insect pathology, molecular entomology, plant biology) is needed to identify molecular targets, interaction mechanisms, and new pathogens for efficient pest management strategies.
PIs:
Baltasar Escriche y Juan Ferré
FUNDING AGENCY:
Conselleria de Educación, Cultura, Universidades y Empleo. Programa Prometeo para grupos de investigación de excelencia. Prometeo 2020 (ref. PROMETEO/2020/010)
Duration: 01/09/2024 – 31/08/2028
Summary:
Animals serve diverse roles in human society, providing companionship, work, sports, and essential food. It is crucial to recognize the economic and ecological importance of livestock farming. Addressing pathogen spread in mass-reared animals is vital for animal welfare, public health, and food safety. This project aims to study the control of parasites in domesticated animals. The objectives include unraveling the determinants for resistance to acaricides in V. destructor, a devastating pest for honeybees, and evaluating the activity of Bt strains against animal parasitic nematodes. The multidisciplinary research group will also perform surveys on the distribution of V. destructor resistance in Spanish apiaries and will carry out screenings to detect Bt strains with nematicidal activity. Moreover, we will undertake studies to optimize Bt protein production and assess their toxicity but also to understand the mode of action and resistance of mites to acaricides and nematodes to Bt. The results will contribute to the design of better management strategies, fostering an ecological and sustainable transition while enhancing livestock farming yield with minimum environmental impact.
PIs:
Joel González Cabrera, Carmen Sara Hernández Rodríguez
FUNDING AGENCY:
Agencia Española de Investigación
Duration: 01/09/2023 – 31/08/2026
Summary:
Varroa destructor causes very serious damage to honeybee colonies worldwide. Parasitized colonies collapse within a few months in the absence of effective control measures. Currently, beekeepers rely heavily on a few active ingredients to control the pest, mainly amitraz, but continue to use pyrethroids and organophosphates. In some cases, they use non-commercial formulations without veterinary advice, which makes the situation even worse. There are now many reports that pyrethroid and organophosphate resistance are widespread, but there are also reports of the lack of efficacy of amitraz in controlling the mite in some areas. However, as far as we know, there is no structured plan or strategy to address this situation from a scientific perspective.
This project will focus on showing the current distribution of pyrethroid and amitraz resistance in a nationwide survey. We will also continue our research on the mechanisms of resistance to the three main groups of acaricides used by beekeepers, amitraz, organophosphates and pyrethroids. Our aim is to describe the actual role of mutations that have been reported to be associated with resistance, but also to detect unknown mechanisms. This information will be used to generate high-throughput diagnostic tools to increase the accuracy of our monitoring and to show a more precise distribution of the resistance phenotype across the country. Finally, due to the very clear demand for new tools to control the mite, we will evaluate the efficacy against Varroa of several active ingredients and essential oils that could increase the number of effective alternatives in the hands of beekeepers in their fight against the parasite. Overall, our proposal should be of great help to the beekeeping community, as they will have, for the first time, accurate information on the resistance profile in their colonies and most likely some more alternatives to fight Varroa. This represents an essential step towards the implementation of an integrated management strategy that will contribute to improved long-term control of the pest.
PIs:
Baltasar Escriche /span>
FUNDING AGENCY:
EU-Ministerio de Ciencia y Tecnologia
Duration: 01/06/2023 – 31/11/2026
Summary:
In all modern agricultural crops, the improvement of vegetable production of economic interest is based mainly on the control of pests and vectors of diseases. Pesticides application involves the use of chemicals with insecticidal, fungicidal, bactericidal properties. However, the expansion of their field application has created serious problems impacting human health and animals. In addition, excessive use of pesticides can leach into soils and water leading to land as well as groundwater pollution and wider biodiversity losses. Some of these products currently used to control pests are extremely toxic in inducing serious human diseases, such as cancer and immune and nervous system disorders.
Current use of plant protection products in conventional and/or organic farming systems should be reconsidered taking in account their side effect on environment, non-target organisms, animal and human health. Such potential risk can be reduced through development, testing and demonstrating of approaches based on products safe for environment and life.
SAFWA project aims to release to the market an innovative solution combining a new competitive biopesticide to cultural trainings aiming to reduce land and water pollution through new agricultural practices. Its specific challenges are to meet the requirement of the EU regulation regarding the registration of safe biopesticides and to provide an environment in which agriculture production contributes to reduce the pollution of the water and the land.
The main goal of SAFWA is to market a new alternative intended to minimize the risk associated with the use of pesticides. Biopesticides, based on two sporulating (BLB1, LIP) and one non sporulating (S22) Bacillus thuringiensis strains, will be used in the field assays to treat olive, citrus and pomegranate trees as well as tomato to protect these different cultures against five pest species. SAFWA will build on the ongoing European project IPM-4-Citrus achievements both at technological and market assessment levels to drive new cultural practices to farmers in 3 experimental farms around the Mediterranean.
PIs:
Salva Herrero
FUNDING AGENCY:
Agencia Española de Investigación
Duration: 01/09/2022-31/08/2025
Summary:
Arbuscular mycorrhizal fungi are soil-borne microorganisms that establish mutualistic associations with roots of most terrestrial plants. This symbiosis results in nutritional and defensive benefits to the host plant, usually conferring protection against biotic stresses, a phenomenon called mycorrhiza-induced resistance (MIR). Previous studies have shown that MIR in tomato confers protection against a certain number of herbivory pests and that the impact of MIR can be variable among different tomato varieties. However, the practical implementation of MIR in integrated pest management (IPM) practices in tomato would need to evaluate its direct impact in the main tomato pests as well as evaluate its indirect impact on third trophic levels, the natural enemies. With this project we aim to evaluate the direct and indirect impact of MIR on one of the main tomato pests, Tuta absoluta. We will determine the level of protection conferred by MIR against T. absoluta in different varieties of tomato. We additionally assess the compatibility of MIR with natural enemies currently contributing to the control of this pest. We will evaluate the influence of MIR on the action of bacterial and viral entomopathogens currently in use for the control of T. absoluta as well as its impact on the predators and parasitoids active against this pest. In addition, the influence of MIR on the interaction of T. absoluta with known and unknown naturally occurring entomopathogens will also be studied, aiming to identify those with potential contributions to the natural regulation of this pest. Obtained results would provide us with the knowledge needed to advise on the use of MIR of tomato and its combination with other natural enemies used for the control of this pest, contributing to the design of most sustainable agricultural practices.
PIs:
Salva Herrero; Joel González-Cabrera
FUNDING AGENCY:
Agencia Española de Investigación
Duration: 01/12/2022-31/06/2025
Summary:
Increase in food production must be aligned with more sustainable approaches reducing the use of agricultural land and water resources, with lower environmental impact and promoting circular agricultural practices. In this direction, insect farming for food and feed have become an essential tool to fulfil current demands on sustainable food production. Indeed, insects constitute a valuable complementary source of proteins and nutrients for humans, while they provide highly nutritious solutions to European livestock and aquaculture producers seeking for new protein sources. The insect rearing industry is an emerging sector across Europe and has the potential to become a strategic link among all parts of the EUs food and feed chains. However, to remain sustainable and cost-effective, insect production urgently needs a major effort in research and innovation to build a parallel body providing innovative strategies and solutions to the sector. In this context, BESTBREED aims to develop new research tools and approaches to improve the efficacy and sustainability of current insect production methods. We will focus on Hermetia illucens, the black soldier fly (BSF), one of the main species used by the insect rearing industry. The project will assess genetic diversity in reared colonies of BSF and develop genetic breeding programs to select for colonies better adapted to the industrial needs without compromising insect fitness, food quality and the susceptibility to disease outbreaks. Therefore, methods for pathogen identification, molecular quantification of genetic diversity and depression will be implemented using high throughput sequencing. This will definitely contribute to a more cost-effective and environmentally sustainable insect rearing industry.
PIs:
Juan Ferré Manzanero and Baltasar Escriche Soler
FUNDING AGENCY:
Agencia Española de Investigación
Duration: 01/09/22 – 31/08/25
Summary:
The Spodoptera genus comprises a number of species whose larvae are especially harmful to agricultural crops. The damage caused by Spodoptera exigua in greenhouse crops in Spain is well known, as well as in open field crops along with Spodoptera littoralis. Recently, a species of this same genus, Spodoptera frugiperda, native to the tropical and subtropical regions of America, has undergone a spectacular expansion due to international trade in agricultural products. Although it has not yet established itself in Europe, it has passed to the African continent, Australia and Asia, causing great damage, especially in maize and sorghum fields, among other crops. The rapid expansion of this pest predicts that sooner or later it will invade Europe. As a matter of fact, S. frugiperda has been declared a priority pest within the group of organisms harmful to plant health by the Ministerio de Agricultura, Pesca y Alimentación from Spain.
In addition to chemical insecticides, Spodoptera spp. can be controlled by bioinsecticides based on the bacterium Bacillus thuringiensis (Bt) and by transgenic crops expressing its insecticidal proteins (Bt-crops). In the EU, the only transgenic crop allowed to be planted is Bt-maize (expressing the Cry1Ab protein from Bt), which confers high protection against corn borers, but is little effective against Spodoptera spp. Second generation of Bt-maize (adopted in non-EU countries) expresses a combination of Cry and Vip3 proteins. The combined expression of several Bt insecticidal proteins, with different modes of action, not only broadens the spectrum of insect species that can be controlled, but also serves to delay the evolution of resistance.
In the last project of both PIs (RTI2018-095204-B-C21), the strategy pursued to obtain an innovative Bt product was to combine, in a single product, two Bt strains, one expressing Cry proteins (which remain insoluble in the parasporal crystal after sporulation) and another with high production of the secretable Vip3A protein. Although the strategy is innovative, an important drawback to scale it up is that independent fermentations are required for the two strains and the recovery of the secreted Vip3 protein is a cumbersome process. However, during the course of the project, we have found out that some strains are capable of retaining the Vip3A protein attached to the spore and the crystals depending on the composition of the culture media.
The present project applies know-how developed through previous projects to the specific problem to control Spodoptera spp. with an innovative approach: the selection of a single strain which retains high amounts of Vip3 in the crystal/spore mixture. A strain with this characteristic will simplify enormously the scale-up of production of an effective Bt product combining the insecticidal properties of Cry and Vip3 proteins. This is one of the objectives of the present project, along with a better understanding of the mode of action of Cry and Vip3 proteins in species of the Spodoptera genus to allow better strategies of control and resistance management of these pests. We will identify the receptors for the most active proteins to these species, which are critical for the toxicity and resistance development. The expected results will provide us with a better knowledge on how to cope with the already existing Spodoptera pests in Spain and prepare us to cope with the likely introduction and establishment of S. frugiperda.
PIs:
Cristina Crava, Lucia Prieto Godino (UK), Jordi Gamir (ES), Felipe Yon (PE)
FUNDING AGENCY:
Human Frontier Scientific Program
Duration: 01/11/2022-31/10/2026
Summary:
Viruses and other pathogens can dramatically modify animal behaviour by altering the host’s nervous system. Famous examples include the zombie ants infected by fungi, or more recently, the neurological effects of SARS-CoV2. How pathogens have evolved to manipulate host behaviour exquisitely, and the molecular and cellular bases behind this manipulation are poorly understood. Furthermore, the host-pathogen interactions are almost exclusively addressed in laboratory under controlled conditions, excluding other players that can shape them in the real world. Tackling these complex, multidisciplinary questions requires in-depth knowledge of ecology and biology of both the host and the pathogen and the ability to genetically manipulate all three ends; the virus, the host and the ecological settings to gain mechanistic insights. Here, we propose to address how viruses alter animal behaviour using as a model the triangle-like interaction between baculovirus, Spodoptera exigua caterpillars and the plants where these latter feed. By coupling genetic manipulation of the three biological systems, transcriptomics, molecular virology, neurophysiology, metabolomics, greenhouse ecological observations and bioassays, we will focus on the alteration of odour-guided behaviors in infected caterpillars and how these interact with ecological factors. Our results will shed light on which host’s biological processes are hitchhiked by the virus to ensure its maximal dispersal and the molecular mechanisms behind this manipulation.
PIs:
Joel González Cabrera
FUNDING AGENCY:
Ministerio de Ciencia Innovación y Universidades
Duration: 01/01/2021 – 30/06/2025
Summary:
Some of the most acute challenges that the world faces are caused by insects and mites that seriously threaten human health and food security. Their control is primarily achieved using insecticides: e.g., malaria prevalence has halved since 2000, saving 660 million lives, with 80% of the reduction being attributable to the use of insecticides. However, both the limited availability of low-risk insecticides (insecticides that only fight the bad bugs) and insecticide resistance represent major threats. So, there is an urgent need to develop novel, safe insecticides. Earlier research pointed to a discriminatory role for the enzyme cytochrome P450 (CYP) in the sensitivity to insecticides. CypTox will exploit the CYP metabolic/detoxification pathway of target and non-target organisms, to develop insecticides, efficient against selected insect & mite major pests and vectors, but highly selective and safe for mammals, pollinators and the environment. Outcomes will also include significantly beyond the state-of-the-art biotechnology-based platforms (high-throughput cell/enzyme- screening assays and in silico pipelines), that will advance research capabilities for future developments of low-risk insecticides. CypTox will provide excellent research training within a creative and flexible environment that actively promotes the integration of academic rigor and commercial pragmatism through mobility between sectors and focused training events. The size and balance of a highly motivated consortium (6 AC/6 non-AC & 3 TC partners; 300 well distributed secondments), the involvement of experienced PIs in Horizon2020 and ERC projects and the modern communication, dissemination and exploitation approaches will ensure efficient implementation and impact, at several levels. Enhanced career perspectives for scientists and researchers will be achieved by building a sustainable multidisciplinary and inter-sectoral network, integrating world leading researchers and stakeholders.
PIs:
Cristina Crava, Jordi Gamir (UJI)
FUNDING AGENCY:
Agencia Española de Investigación
Duration: 01/09/2021-31/08/2024
Summary:
Plants have evolved different strategies for molecular recognition to respond to environmental threats. Early recognition of self- and non-self damage is essential for the rapid and efficient activation of defense mobilization and immune responses. Damage-associated molecular patterns (DAMPs) are endogenous molecules released from disrupted or dying cells that activate plant innate immunity by interacting with pattern recognition receptors. On the other hand, chewing insects cause massive damage by crushing plant tissue during feeding, releasing a vast array of cues that may mobilize plant defenses. These molecules are known as herbivore-associated molecular patterns (HAMPs). Molecular recognition of HAMPs activates inducible plant defenses, leading to impaired insect growth. A few studies have demonstrated that other trophic players, such as insect-associated microbes present in regurgitant, can also be perceived by plants and may activate or suppress inducible defenses, in a manner highly dependent on the specific host plant–herbivore interaction. Recent research on molecular pattern applications proposes the use of these molecules (mainly DAMPs) as an alternative to traditional pesticides and highlights the need to understand the complex mechanisms triggered upon damage recognition.
The main goal of this project is to identify self- and non-self damage signals that potentiate defense responses and enhance plant protection against herbivorous insects. We also propose to study the metabolomic reconfiguration of tomato plants after DAMP perception during their interaction with the chewing insect Spodoptera exigua, and to explore the role of S. exigua-associated microbes in inducing plant defenses and mediating fitness consequences after DAMP-induced defense mobilization. The outcome of this project will reveal new biological inducers that can be translated into practical applications to improve plant resistance against caterpillars, reducing the reliance on harmful pesticides.
PIs:
Juan Ferré Manzanero
FUNDING AGENCY:
Conselleria d’Innovació, Universitats, Ciència i Societat Digital de la Generalitat Valenciana, Programa Prometeo para grupos de investigación de excelencia. Prometeo 2020 (ref. PROMETEO/2020/010)
Duration: 13/11/20 – 31/05/24
Summary:
Most studies on Bt insecticidal proteins to date have focused on those of the Cry1A, Cry1F, Cry2A, and Cry3 families, given that these proteins were the first to be discovered and characterized in the late 1960s, and whose genes were subsequently successfully introduced and expressed in plants («Bt crops»). However, much less attention has been paid to other Bt insecticidal proteins, such as those of the Vip3 family, despite the fact that the vip3Aa gene has already been introduced into Bt crops as a complement to the cry genes. Furthermore, studies on the mode of action of Cry proteins other than those mentioned above are relatively few.
In previous projects (PROMETEOII/2015/001 and AGL215-70584-C2-R), we have generated new information on the mode of action of Vip3 proteins, discovered a new family of insecticidal proteins (Cry37-like), and contributed to a better understanding of the biochemical basis of resistance to Bt toxins.
In the current project, we will continue previously initiated lines of research to further contribute to a better understanding of how Bt toxins (Vip3A and Cry) function and interact with each other and with other molecules, and how insects can develop resistance to them. The structural and functional analysis of Vip3 family proteins will be a primary objective, as will the study of the mode of action of understudied Cry proteins found in our Bt collections. A better understanding of the mode of action of these proteins will help us understand the basis of resistance to them in insect pests.
PIs:
Cristina Crava
FUNDING AGENCY:
Conselleria de Educación, Cultura, Universidades y Empleo; Generalitat Valenciana
Duration: 01/07/2020-31/06/2024
Summary:
PIs:
Salva Herrero (from the Subproject)
FUNDING AGENCY:
EU Framework Programme HORIZON 2020
Duration: 01/011/2019-31/10/2024
Summary:
Successful application of mass reared insects heavily relies on culturing large insect colonies. In such “insect factories” insect pathogen emergence is easily triggered leading to extensive economic losses. To remain sustainable, achievable, and cost-effective, insect production urgently needs to become more resilient to the effects of a large range of pathogens (i.e. bacteria, fungi, viruses and microsporidia) In-depth knowledge on insect pathogens is paramount to both mitigate for and prevent such disease outbreaks. The INSECT DOCTORS network trains promising young scientists to develop the knowledge, technical skills and tools to diagnose and manage disease problems in commercial insect production systems. INSECT DOCTORS is a European Joint Doctoral Programme (EJD) funded in the framework of the H2020 Marie Skłodowska-Curie ITN programme. The program started in 2019 and officially ended in November 1, 2024. The training programme was based on close interaction between the academic and industrial sectors. 15 PhD candidates received their training throught this network and executed innovative research projects at participant’s locations. Twelve candidates have meanwhile successfully defended their PhD thesis. The others are nearing their PhD thesis submission date.
PIs:
Joel González Cabrera
FUNDING AGENCY:
Agencia Española de Investigación
Duration: 01/01/2019 – 31/12/2022
Summary:
The devastating effect caused by the ectoparasitic mite Varroa destructor is considered one of the most important problems for modern apiculture. The damages caused are so high that 100 % of parasitized colonies will collapse in 2-3 years in absence of an effective control in place. Beekeepers are relying heavily in a few active ingredients to control the pest, mainly pyrethroids, coumaphos or amitraz. In some cases, they are using non-commercial formulations with no veterinarian advice, which turns the situation even worse. Currently, there are many spots of resistance to these active ingredients but there is very little information about the factors contributing to the spread of this phenomenon.
This project will focus on the study of several aspects influencing the evolution of resistance to acaricides in V. destructor. We plan to explore the possible implication of acaricide residues in beeswax as major drivers for resistance evolution, the impact of mutations in the target site of pyrethroids on the mite fitness, and the efficacy of new active ingredients on Spanish populations of V. destructor. Overall, this should represent an essential step towards the implementation of an Integrated Pest Management strategy that may contribute to a long-term effective management of the pest.
PIs:
Juan Ferré Manzanero and Baltasar Escriche Soler
FUNDING AGENCY:
Agencia Española de Investigación
Duration: 1/1/19 – 31/12/21
Summary:
Most studies on the insecticidal proteins from Bt carried out to date have focused in those of the families Cry1A, Cry1F, Cry2A and Cry3, since these were the first to be discovered and characterised at the end of 1960s and whose genes have been introduced and expressed in plants (Bt crops). However, much less attention has been paid on other Bt insecticidal proteins, such as those of the Vip3 family, despite the fact that the vip3Aa gene has already been introduced in Bt crops as complementary to the cry genes. Furthermore, studies on the mode of action of Cry proteins other than those mentioned above are relatively little abundant.
In the previous project (AGL215-70584-C2-R) we have developed a new bioinsecticide based on the combination of two Bt autochthonous strains, which complement to each other regarding the Cry proteins they express (and, therefore, have complementary insecticidal activities), in addition to express Vip3Aa proteins. We also studied the mode of action of Cry and Vip proteins, the effect of synergistic compounds and the biochemical basis of resistance to Bt toxins in insect resistant strains.
In the current project, we want to continue with these research lines, to further contribute to the better knowledge on how Bt toxins function and interact among themselves and other molecules, and to optimise a Bt-based product to the point of being able to transfer the results so that it can reach the market.
The mode of action of proteins of the Vip3 family is little known. Since the two selected strains in the present project express Vip3Aa proteins, a first goal will be to study the structural features of Vip3Aa that are critical for its mode of action. We have generated chimeras by domain shuffling and we have a collection of clones containing amino acid substitutions of the wild type protein. This valuable material will be used to further study the structure-function of the Vip3 proteins.
The strain selected in the previous project Lo013.1 showed partial sequences of genes that are not expressed in standard culture media. These genes belong to very poorly studied families and could be expressed under appropriate medium conditions. As a second goal we will clone and express these cry genes to determine the spectrum of activity and their mode of action of the proteins they encode. In parallel, we will approach the general mode of action developing methodologies for molecular dissection of the successive events, such as the oligomerization, binding to receptors, and the cell death pathway. The interaction of synergistic compounds will be also addressed.
Since evolution of resistance by insect populations is the major threat to the use of Bt insecticides and Bt crops, it is of paramount importance to study the ways insects develop resistance against Bt toxins with the aim of implementing strategies to avoid or delay it. The S1 group has long been a reference laboratory for the analysis of resistant insects, especially because of the use of 125I in labelling toxins for binding studies. A third goal will be to continue this research line by analysing Cry and Vip resistant strains from collaboration laboratories all over the world.
PIs:
Joel González Cabrera
FUNDING AGENCY:
Ministerio De Agricultura, Pesca y Alimentación
Duration: 01/08/2017 – 31/07/2019
Summary:
El efecto devastador que ejerce el ácaro ectoparásito Varroa destructor sobre las colonias de las abejas de la especie Apis mellifera es considerado uno de los principales problemas de la apicultura actual. La pérdida de las colonias parasitadas puede ser del 100 % en 2-3 años si no se toman medidas eficaces de control. Los apicultores continúan aplicando de forma intensiva, y muchas veces sin control veterinario, un reducido grupo de materias activas, fundamentalmente de estos tres grupos de plaguicidas: piretroides (tau-fluvalinato y flumetrina), organofosforados (cumafós) y amidinas (amitraz). Actualmente, existen múltiples focos de resistencia a estos compuestos sin que exista un plan con directrices definidas para detectar y cuantificar sus niveles y distribución.
En el caso de los piretroides sintéticos, se conoce que la resistencia en las poblaciones europeas analizadas es debida a la mutación L925V, localizada en el sitio propuesto para el anclaje del piretroide a la molécula diana. La distribución de esta mutación en las provincias implicadas se determinará a través ensayos diagnóstico de alto rendimiento puestos a punto con anterioridad en nuestro laboratorio. Además, en nuestro laboratorio hemos optimizado un método de bioensayo que nos permite cuantificar de forma rápida y precisa la frecuencia de ácaros resistentes a cumafós y amitraz en una colmena determinada.
Esta propuesta pretende ser la continuación del proyecto 20180020000920, financiado en la pasada edición de esta línea de ayudas. Esta es la primera iniciativa en el ámbito del estudio de la resistencia a los acaricidas en las poblaciones de V. destructor en una Comunidad Autónoma, una propuesta pionera que tiene como objetivo general sentar las bases para generar un protocolo de actuación que conlleve a la Gestión Integrada del ácaro. El trabajo realizado permitió evaluar 72 muestras que abarcaban las 3 provincias de la Comunidad Valenciana, así como 2 explotaciones de Albacete y Teruel. Los resultados obtenidos reflejan con un alto nivel de precisión la situación en cada una de las explotaciones y serán utilizados como referencia para evaluar la evolución de la problemática cuando se generen los resultados de este período.
En esta nueva propuesta se pretende continuar con los análisis de la resistencia a las tres materias activas. Es muy necesario continuar y ampliar el alcance de nuestro rastreo, por lo que en esta ocasión se ampliará el período de muestreo tanto en otoño como en primavera para garantizar el envío de muestras con un grado de parasitismo suficiente y así obtener un número de ácaros idóneo para la realización de los ensayos en un porcentaje mayor de las muestras.
La transferencia y difusión de nuestros resultados, tanto a la comunidad científica como entre los apicultores y reguladores, permitirá una mejora considerable en la toma de decisiones a la hora de seleccionar las metodologías y estrategias más adecuadas para controlar al parásito. Creemos que esto supondrá un avance importante hacia el logro de una apicultura sostenible, segura y de calidad.
PIs:
Joel González Cabrera
FUNDING AGENCY:
Foundation for Food and Agriculture Research
Duration: 01/02/2018 – 31/01/2021
Summary:
Varroa destructor remains one of the most critical threats to global beekeeping due to its direct damage to honey bees and its role as a vector of harmful viruses. Although chemical control has historically been the most effective management tool, resistance has emerged against the major varroacides—including tau-fluvalinate, coumaphos, and amitraz—largely due to prolonged use, inconsistent regulation, and past off-label applications. Natural compounds such as oxalic acid are safer for bees but show limited efficacy when brood is present. As a result, beekeepers currently face a severe shortage of safe, effective, and resistance-breaking tools.
This project aims to rapidly deliver new varroacides that are both effective and have minimal resistance potential. It is structured around three major objectives: (1) screening a broad array of synthetic and natural compounds with acaricidal properties through laboratory and semi-field trials; (2) identifying biochemical and molecular mechanisms underlying resistance to existing varroacides, including mutations in target sites and enhanced detoxification pathways; and (3) streamlining the registration process for promising compounds in the U.S. and Canada under FIFRA and Canadian Pest Control Products regulations.
The methodology includes standardized toxicity assays on Varroa mites and honey bees, followed by field trials using controlled colonies to evaluate efficacy, bee safety, and residue profiles. Surviving mites will be analyzed to identify resistance-associated mutations and detoxification activities, integrating molecular sequencing, enzymatic assays, and comparative analyses across regions. Close collaboration with EPA and PMRA will ensure that generated data are directly applicable to regulatory requirements and facilitate fast-track registration when appropriate.
By combining chemical screening, resistance research, and regulatory alignment, this project will produce a pipeline of novel, science-based tools to enhance integrated pest management programs, slow resistance evolution, and strengthen the long-term sustainability of beekeeping in North America.
PIs:
Joel González Cabrera
FUNDING AGENCY:
Agencia Española de Investigación
Duration: 01/01/2016 – 31/12/2018
Summary:
The devastating effects caused by the ectoparasitic mite Varroa destructor are considered one of the most important problems for modern apiculture. The damages caused are so high that 100 % of parasitized colonies will collapse in 2-3 years in absence of an effective control in place. Beekeepers are relying heavily in a few active ingredients to control the pest, mainly pyrethroids (tau-Fluvalinate or Flumethrin), Coumaphos or Amitraz. In some cases, they are using non-commercial formulations with no veterinarian advice which turns the situation even worse. Currently, there are several spots of resistance to these active ingredients but there is no dedicated plan in place to detect and quantify their levels and distribution.
This proposal is aiming to make a significant contribution to the elucidation of resistance mechanisms in V. destructor populations and to develop and deploy high throughput diagnostics assays to detect resistant mites. Transferring this information to the beekeepers and regulators should help in designing more effective strategies to control the mite. It is already known that resistance to synthetic pyrethroids in the European populations tested so far is correlated with the mutation L925V mapping in the putative binding site of these compounds. Samples collected all over the country will be analysed using a high throughput DNA-based TaqMan diagnostic assay already set up to determine the distribution and frequency of the mutation. In case there are resistant samples negative for the mutation, further throughout analysis will be performed in order to elucidate the possible mechanism(s) involved.
There is no information available regarding the Resistance mechanisms to Coumaphos or Amitraz in this species. Samples with known resistant phenotype will be analysed to search for polymorphisms in the targets that might be causing resistance as well as for the influence of detoxifying enzymes in this phenomenon. We believe that the combination of transcriptomic approaches with PCR amplification of target molecules and sequencing is the best strategy to accomplish these objectives.
Finally, we will use the information generated in previous tasks to design new high throughput diagnostic assays to accurately identify resistant mites in the populations.
Identifying the resistance mechanisms should be the first step to design and implement Integrated Pest Management strategies. The development of robust, quick and accurate detection methodologies is currently needed in the Spanish as well as the European scenarios. Transferring our results to the scientific community, the beekeepers and regulators will improve the decision-making process to select the best alternatives for controlling the pest. We believe that our results should pose a step forward in the way to make a better, safer and sustainable apiculture.
