University of Valencia - Faculty of Biological Sciences
Department of Genetics

Biochemical Genetics and Biotechnology Research Unit

Areas of research

last update 2010-10-6


The group of Biochemical Genetics and Biotechnology is involved in the study of the microbial control of insect pests using
Bacillus thuringiensis and baculovirus. In the following sections, there are some general ideas on our field of work, as well as the specific lines of research on which we are working.

 

1) Bacillus thuringiensis AND BACULOVIRUS FOR THE MICROBIAL CONTROL OF INSECT PESTS

One of the agents most used in the microbial control of pests is the bacterium Bacillus thuringiensis. During sporulation, this bacterium synthesises especial proteins that aggregate to form a parasporal crystal which can reach, in some strains, the same size as the spore. When insects ingest the sporulated bacterium, in addition to the spore they also ingest the crystal. This is dissolved in the intestine where it releases its protein components (protoxins) which, normally, have to be activated by intestine proteases to their toxic final form. The toxin then binds to receptors in the epithelial membrane of the intestine forming pores in the cells which eventually kills the insect. This poisoning facilitates germination of the spore and invasion of its host.

The other agents, baculovirus, are viruses that infect invertebrates, mostly insects from the order Lepidoptera. Also known as nucleopolyhedroviruses, they are obligate pathogens that are characterized by their rod-shaped nucleocapsids, each of which contains a single circular molecule of double-stranded DNA. The nucleocapsid is wrapped in a lipoprotein membrane to form virions, that are occluded by a protein matrix to form the occlusion body (OB). Each OB can contain dozens of virions.  The majority of the currently identified baculovirus have been isolated from a few hundred species of insects, mainly Lepidoptera and phytophagous Hymenoptera, many of which are important pests of agricultural crops and forests. The infection by baculovirus starts when the insect ingests the OB. This is dissolved in the intestine with the consequent release of the virions (also know as occluded derived virus, ODV).  The released ODV will fuse to the columnar epithelial cell membrane of the host intestine entering into the cell. Once into the cell, the nucleocapsids are transported to nucleus where the viral transcription and replication takes place. A novel viral form will be produced (budded virus, BV) in these infected cells. These forms will bud out of the cells spreading the infection systemically. In the late stage of the infection the insect disintegrates and millions of BV and OB are released to the environment, starting a new cycle.

Some advantages of using these pathogens in the fight against insects are, on the one hand, their specificity, since one can target the pest insect without affecting the beneficial insect populations and, on the other hand, they are totally innocuous to organisms other than insects, including humans. These characteristics make the insecticides based on B. thuringiensis and baculovirus a resource very appreciated from the standpoint of the organic farming. As a matter of fact, they are of the very few insecticides allowed in this type of agriculture. Another advantage which B. thuringiensis has is that, because the toxin is a protein, genes can be manipulated in the laboratory in such a way that the mutant protein becomes more efficient or even acquires toxicity to control new pests. However, the reason why this bacterium is so popular is because of its use in genetic engineering, since its genes can be integrated in plant genomes and then these plants produce the insecticidal protein and become resistant to the insects that normally feed on them.

The search for new B. thuringiensis genes that codify for new insecticidal proteins will allow to broaden the spectrum of action of B. thuringiensis-based insecticides. This is of great interest not just to fight pests that are not controlled at present by this type of insecticides, but to obtain toxins that will maintain their effectiveness to control insect populations when these start to develop resistance to toxins currently in use from this bacterium.

The problem of insect resistance is a very important one as it can render an insecticide obsolete in few years. This problem does not only affect chemical insecticides, but it also affects microbial insecticides. An understanding of the mechanisms by which B. thuringiensis toxins or baculovirus act, and by which an insect can become resistant to them, can help to design strategies to prevent resistance from appearing. The results of this type of research are very useful to design strategies for the utilisation of B. thuringiensis-based insecticides to minimise the possibility of resistance appearing and, in this way, to ensure that this insecticide, which has such useful characteristics, continues to be useable. But this understanding is especially relevant in the context of the design of insect resistant transgenic plants, since the correct selection of genes (which codify toxins) to be introduced in a plant will depend on their mode of action. A plant expressing two toxins that use the same target site for their action will provoke the appearance of resistance in the pest insects much faster than one expressing two toxins that use different target sites.

 

2) RESEARCH LINES AND GOALS

The main goal of this research group consists on the control of insect pests by the use of microbial insecticides based on the bacterium Bacillus thuringiensis and baculovirus. The group works on three research lines and their objectives are summarised below.

 

1. Resistance to bioinsecticides

General objective: To study the potential of insects to develop resistance to toxins from B. thuringiensis and the genetic and biochemical basis of this resistance. This is a basic line of research, though with an applied projection. It was with this line that the most senior members of the group began to work with B. thuringiensis, at the end of 1989.

One of the objectives pursued within this line of research is the study of the mode of action of the toxins from B. thuringiensis to, in this way, be able to understand the mechanisms of resistance that the insects can generate against these toxins. The understanding of how these toxins act in a particular pest also allows us to make predictions on the possible appearance of cross-resistance to other B. thuringiensis toxins. Another objective is the detailed understanding of the resistance mechanism occurring in insect strains resistant to B. thuringiensis formulations.

The species which we have most studied, and the one that we are still most actively studying, is the diamondback moth, Plutella xylostella, which is the only species to date to evolve resistance to B. thuringiensis in the field (though not to transgenic crops). However, our interest covers any species that has evolved resistance to B. thuringiensis toxins. So far we have worked with laboratory resistant strains of the lepidopterans Plodia interpunctella (Indianmeal moth), Trichoplusia ni (cabbage looper), Ostrinia nubilalis (corn borer) and Heliothis virescens (tobacco budworm), and we have performed studies on the mode of action in other lepidopterans, such as Helicoverpa armigera, Phthorimaea operculella (potato tuber moth), Mamestra brassicae, Spodoptera exigua and Cacyreus marshalli (geranium bronze). We have also worked with the dipteran Bactrocera oleae (olive fly).


2. Development of novel bioinsecticides

General objective: To find B. thuringiensis strains and genes with novel insecticidal properties. These are activities concerned with practical applications, since the final goal is to obtain industry-transferable results. This research line was started in 1994.

One of the objectives is the development of bioinsecticides based on new strains of B. thuringiensis with high activity against pest insects. We plan to use natural strains with high activity or with a broader insecticidal spectrum, as well as hybrid strains obtained by means of plasmid transfer. We have currently a collection of around 650 isolates of B. thuringiensis. Another objective is the isolation and characterisation of novel genes in this bacterium codifying proteins with high insecticidal properties.

In collaboration with the Departamento de Producción Agraria of the Universidad Pública de Navarra, we have found and characterised five new B. thuringiensis serovars, whose respective type strains have been deposited in the International Entomopathogenic Bacillus Center of the Pasteur Institute in Paris. As a consequence of this collaboration we have filed two patents those with the most toxic isolates against lepidopterans. There are currently two insecticidal formulations based on these isolates in the process of getting registration to commercialise them.

With this line of research we collaborate with a number of companies, within and outside Spain. Among the services offered we can mention the quality control of the products based on B. thuringiensis, as well as studies aimed at getting these products registered.


3. Insect-pathogen interaction

Insects represent one of the most successful examples of adaptive evolution, being able to colonize almost all ecological niches. Consequently, they had to cope with an extremely large variety of pathogens, including baculovirus and B. thuringiensis. The evolution of insects as well as the evolution in their pathogens has followed parallel pathways. Changes in the insect that contributed to reduce the effect of the pathogen have been responded by adaptations of the pathogen trying to escape to the insect defence. In order to overcome, or at least, to minimize the pathological effect, insects have developed different mechanism. Among the known mechanisms, some of them promote the activation of detoxification and damage repair mechanisms. Other mechanisms include the synthesis and secretion of antimicrobial peptides and degradation enzymes, phagocytosis, melanization, cell apoptosis, or cell sloughing, among others (some of them probably still unknown). The activation of these mechanisms reduces the chances of pathogens to extend their infection and can be responsible of the development of insect resistance.

By combination of SSH (Suppressive Subtractive Hybridization) with DNA-microarray we are trying to identify the insect’s elements involved in the response to these pathogen and as consequence, determining the mechanism of insect response to pathogens. Information about the mechanism of insect defence can be very useful for the identification of the possible mechanisms of insect resistance to baculovirus or B. thuringiensis. Moreover, the obtained information can be used for optimizing the use of these pathogens as a pest control agent. In collaborations with the group of Dr. Ruud de Maagd (Plant Research International, The Netherlands) we are currently analyzing the interaction between S. exigua and B. thuringiensis (or its toxins). Similarly, in collaboration with Dr. Karl Gordon (CSIRO Entomology, Australia) we are analyzing the response of H. armigera to its baculovirus (HaSNPV) and also to B. thuringiensis toxins. 

 

 

3) FUNDING SOURCES AND RESEARCH PROJECTS:

The projects on which we work have been funded by the European Union within all Framework Programmes since the third. The group has also received non-interrupted funding from the Ministry of Science and Education (or from that of Science and Technology) and from the Generalitat Valenciana (Autonomic Government) competing with competitive projects. Other sources of funding have been contracts and agreements with private companies such as Bayer BioScience, Industrias AFRASA and Biológicas Canarias, among others. The most relevant projects in the last 10 years are shown below:

 

Title of the project: Introduction of resistance to Cacyreus marshalli in Pelargonium zonale by genetic transformation with Bacillus thuringiensis

Funding agency: Ministerio de Educación y Ciencia (Proyectos de I+D del programa FEDER) (FD1997-0917-C02-01).

Participant Centres: Universitat de València, Universidad Politécnica de Valencia and Fundación PROMIVA (Manises, Valencia)

 

Title of the project: Bacillus thuringiensis resistance management in cotton pests.

Funding agency: Ministerio de Educación y Cultura (Plan Nacional de I+D, Programa Nacional de Recursos y Tecnología Agroalimentarias) (AGL2000-0840-C03-01).

Participant Centres: Universitat de València, Universidad de Córdoba and Universidad Pública de Navarra.

 

Title of the project:  Engineering transgenic pelargoniums for resistance to fungi and insects

Funding agency: Ministerio de Ciencia y Tecnología (Plan Nacional I+D+T, Programa de Fomento de la Investigación Técnica, PROFIT) (FIT-010000-2001-87).

Participant Centres: Fundación PROMIVA (Majadahonda, Madrid), Instituto de Biología Molecular (CSIC, Barcelona) and Universitat de València.

 

Title of the project:  Engineering transgenic ornamental Pelargonium resistant to the infection by pathogenic fungi or to insect attack

Funding agency: Ministerio de Ciencia y Tecnología (Plan Nacional I+D+T, Programa de Fomento de la Investigación Técnica, PROFIT) (FIT-010000-2002-13).

Participant Centres: Fundación PROMIVA (Majadahonda, Madrid), Instituto de Biología Molecular (CSIC, Barcelona) and Universitat de València.

 

Title of the project:  Protecting the benefits of Bt-toxins from insect resistance development by monitoring and management.

Funding agency: Comisión Europea (Programa Quality of life and management of living resources). (QLTR-2001-01969)

Participant Centres: Aachen University of Technology (Aachen, Germany), CIB-CSIC (Madrid), INRA La Minière (Guillantcourt, France), Università degli Studi (Milán, Italy), Slovak Agricultural Unviersity (Nitra, Slovakia), Aristotle University of Thessaloniki (Salónica, Greece), Fraunhofer Institute for Molecular BIology and Applied Ecology (Schmallenberg, Germany), University of Melbourne (Parkville, Australia) and Universitat de València.

 

Title of the project: Microbial alternatives to agrochemicals in plant protection.

Funding source: Oficina de Ciencia y Tecnología de la Generalitat Valenciana (OCYTGV). (CTGA/2002/03/01)

Participant Centres: Universitat de València.

 

Title of the project:  Biochemical and genetic analysis of resistance to Bacillus thuringiensis toxins in Plutella xylostella.

Funding agency: Consejo Nacional de Ciencia y Tecnología de Méjico (CONACYT) (Ref. 38040-N).

Participant Centres: Universidad Autónoma de Nuevo León (Méjico) and Universitat de València.

 

Title of the project:  Development of a new bioinsecticidal product from a novel authoctonous strain of Bacillus thuringiensis.

Funding agency: Ministerio de Ciencia y Tecnología (Proyecto de Estímulo a la Transferencia de Resultados de Investigación, PETRI) (PTR1995-0633-OP).

Participant Centres: Universitat de València and Industrias AFRASA, S.A.

 

Title of the project:  Bases of resistance to Bt toxins in lepidopteran pests.

Funding agency: Ministerio de Ciencia y Tecnología (Plan Nacional de I+D+I, Programa Nacional de Recursos y Tecnología Agroalimentarias) (AGL2003-09282-C03-01).

Participant Centres: Universitat de València, Universidad de Córdoba and Universidad Pública de Navarra.

 

Title of the project:  Grant for research groups.

Funding agency: Conselleria de Cultura, Educació i Esport de la Generalitat Valenciana (GRUPOS2004-21).

Participant Centres: Universitat de València.

 

Title of the project:  Resistance bases to the insecticidal crystal proteins from Bacillus thuringiensis in lepidopteran populations.

Funding agency: Conselleria de Cultura, Educació i Esport de la Generalitat Valenciana (GV04B-165).

Participant Centres: Universitat de València.

 

Title of the project: Prevention of resistance to baculovirus in Spodoptera exigua.

Funding agency: Ministerio de Educación y Ciencia (Plan Nacional de I+D+I, Programa Nacional de Recursos y Tecnología Agroalimentarias) (AGL2005-0709-C03-03/AGR).

Participant Centres: Universitat de València and Universidad Pública de Navarra (Pamplona)

 

Title of the project:  Bases of resistance to Bacillus thuringiensis toxins in lepidopteran pests.

Funding agency: Conselleria de Empresa, Universidad y Ciencia de la Generalitat Valenciana, programa de Ayudas complementarias para proyectos de I+D+I (ACOMP06/133).

Participant Centres: Universitat de València, Universidad de Córdoba and Universidad Pública de Navarra (Pamplona).

 

Title of the project:  Resistance management to Bacillus thuringiensis insecticidal proteins.

Funding agency: Ministerio de Educación y Ciencia (Plan Nacional de I+D+I, Programa Nacional de Recursos y Tecnología Agroalimentarias) (AGL2006-11914).

Entitats participants: Universitat de València.

 

Title of the project:  Building a net of research groups and centres to assist the scientific-technical needs of companies in the Valencian Comunity (Red Valenciana de Investigación Vinculada).

Funding agency: Conselleria de Empresa, Universidad y Ciencia de la Generalitat Valenciana (ref. ARVIV/2007/090).

Participant Centres: Universitat de València and other universities and research centres from the Comunidad Valenciana.

 

Title of the project: Host response to baculovirus infection in Helicoverpa armigera.

Funding agency: Unión Europea (programa Structuring the ERA).

Participant Centres:  Universitat de València

 

Title of the project: Stablishing collaboration links in the research on Bacillus thuringiensis based bioinsecticides.

Funding agency: Programa de Cooperación Interuniversitaria de la Agencia Española de Cooperación Internacional (AECI) el marco del PCI-Mediterráneo 2007.

Participant Centres: Universitat de València and Centre de Biotechnologie de Sfax (Tunisia)

 

Title of the project:. Specific binding of Bt toxins to midgut membranes from sweetpotato weevil, Cylas spp.

Funding agency: The Rockefeller Foundation (07-ENT-367314-VAL).

Participant Centres:  Universitat de València, Auburn University (USA) and Centro Internacional de la Papa (Peru).

 

Title of the project: Mode of action of Bacillus thuringiensis VIP proteins in Helicoverpa armigera and Spodoptera exigua.

Funding agency: Unión Europea (programa Structuring the ERA).

Participant Centres: Universitat de València

 

Title of the project: Genes of response to the baculovirus of Spodoptera exigua, applications for the improvement of its insecticidal properties.

Funding agency: Ministerio de Ciencia e Innovación (Plan Nacional de Investigación Científica y Desarrollo e Innovación Tecnológica) (AGL2008-05456-C03-03).

Participant Centres: Universitat de València and Universidad Pública de Navarra.

 

Title of the project: Development of a novel bioinsecticide based on Pseudomonas fluorescens.

Funding agency: Conselleria de Empresa, Universidad y Ciencia de la Generalitat Valenciana (ref. GVPRE/2008).

Participant Centres: Universitat de València.

 

Title of the project: Secretable toxins from Bacillus thuringiensis for the control of lepidopterans.

Funding agency: Programa de Cooperación Interuniversitaria de la Agencia Española de Cooperación Internacional para el Desarrollo (AECID) en el marco del PCI-Mediterráneo 2008 (A/017413/08).

Participant Centres: Universitat de València and Centre de Biotechnologie de Sfax (Tunisia).

 

Title of the project: Second generation insecticidal proteins from Bacillus thuringiensis.

Funding agency: Ministerio de Ciencia e Innovación, Programa Hispano-Brasileño de Cooperación Interuniversitaria (PHB2008-0113-PC).

Participant Centres: Universitat de València and Universidade Estadual Paulista (Brasil).

 

Title of the project: Resistance to African sweetpotato weevils using biotechnology.

Funding agency: The Rockefeller Foundation (08-EPP-368722-UV).

Participant Centres: Universitat de València, Auburn University (USA) and Centro Internacional de la Papa (Peru).

 

Title of the project: Resistance management of Bacillus thuringiensis insecticidal proteins.

Funding agency: Conselleria d’Educació de la Generalitat Valenciana, programa de Ayudas complementarias de I+D+i a grupos de calidad contrastada para completar el desarrollo de proyectos de I+D vigentes (ref. ACOMP/2009/313).

Participant Centres: Universitat de València.

 

Title of the project: Mode of action of secretable insecticidal proteins from Bacillus thuringiensis.

Funding agency: Ministerio de Ciencia e Innovación (Plan Nacional de I+D+I, Programa Nacional de Investigación Fundamental) (AGL2009-13340-C02-01).

Participant Centres: Universitat de València y Universidad Pública de Navarra.

 

Title of the project: Resistance management of Bacillus thuringiensis insecticidal proteins.

Funding agency: Conselleria d’Educació de la Generalitat Valenciana, programa de Ayudas para grupos de calidad contrastada, del programa Gerónimo Forteza. (ref. FPA/2010/011).

Participant Centres: Universitat de València

 

Title of the project: Sweet Potato Action for Security and Health in Africa (SASHA)

Funding agency: Bill and Melinda Gates Foundation (BMGF)

Participant Centres: Universitat de València, Centro Internacional de la Papa (CIP), consorcio de países africanos