World's Top 2% Scientists (Stanford University)
I completed my bachelor's studies in Biological Sciences at the University of Navarra in 1988. Subsequently, I earned my PhD in Microbiology at the Center for Molecular Biology (CSIC-UAM) of the Autonomous University of Madrid in 1992. Afterwards, I spent three years conducting research in the laboratory of Professor Pascale Cossart at the Pasteur Institute, focusing especially on the actin-based motility genetics of Listeria monocytogenes. In 1997 I returned to Spain as a microbiology professor at the Public University of Navarra (UPNA) in Pamplona. The following year, in 1998, I obtained a permanent academic position in microbiology and began my research line dedicated to the study of bacterial biofilm formation at the Institute of Agro-Bio Technology, a mixed center between UPNA/CSIC. In 2008, I obtained a Chair in Microbiology through the habilitation process and, at the end of 2015, assumed the position of director of Navarrabiomed, a recently created biomedical research center located in Pamplona. I have always been aware of the need and importance of transferring research results to society. Therefore, in 2011 I co-founded the biotechnology company RECOMBINA S.L. (Pamplona). I have been Principal Investigator in nine consecutive nationally funded projects, funded by the Spanish Ministry of Economy, Industry and Competitiveness, as well as in four European Union grants (6th and 7th Framework Programs). Throughout my career, I have supervised 19 PhD students; several of whom currently lead their own research groups. Currently, the Microbial Pathogenesis Unit is currently focused on investigating: The global function of the sensory system of two components in Staphylococcus aureus.
The c-di-GMP sensory network in Salmonella enteritidis. The regulation of transcription
through overlapping mRNA of neighboring genes and its degradation mediated by RNase III. The synthesis of the components of the biofilm matrix. Among the key findings of our work are:
The identification of a protein family, called Bap, that promotes biofilm formation in various bacterial species through the adoption of an amyloid conformation. The finding that the two-component sensory system is dispensable for the growth of S. aureus under laboratory conditions. The demonstration of a mechanism of transcriptional control in bacteria based on the overlap of mRNAs from neighboring genes and their consequent digestion by RNase III activity. The identification of a new genetic organization in bacteria, which we have called discontiguous operon.
The “Joint Action on integrating prevention, testing and link to care strategies across HIV, Viral Hepatitis, TB & STIs in Europe” (INTEGRATE) has the overall objective to increase Integrated early diagnosis and linkage to prevention and care of HIV, viral hepatitis, TB and STIs in EU Member States by 2020.
A number of tools have been developed to reduce transmission, optimize early diagnosis and linkage to care for one or more of these four diseases. INTEGRATE will map relevant existing tools for cross-linking. A peer-review process will identify which of these tools are complimentary or redundant for other disease(s), and which could be adapted or require further innovation.
The objective of the Microbial Pathogenesis Research Unit is to understand, at the molecular level, how pathogenic bacteria grow adhered to the surface of medical devices or tissues, producing infections that do not respond to antibiotic treatment and therefore often become chronic. To study this form of bacterial growth, which is called biofilm, the group employs genetic engineering approaches, omics technologies, synthetic biology and animal experimentation models. The ultimate aim of their research is to identify the critical elements of the biofilm formation process in order to prevent its formation, eliminate already formed biofilms, improve existing treatments or promote the formation of biofilms of non-pathogenic bacteria for therapeutic purposes.
Research lines:
• Signal transduction mechanisms in bacteria.
Development of bacteria for therapeutic purposes and identification of new targets for the treatment of infections.
• Study of bacterial adhesion to abiotic surfaces, such as medical implants and tissues.
The Microbial Pathogenesis Unit of Navarrabiomed-Public University of Navarra (UPNA) has found a new genetic organisation in bacteria that helps better understand bacterial biology. The study of this genetic architecture was published in Proceedings of the National Academy of Sciences of the United States of America (PNAS).
Research background
In 1961, François Jacob and Jacques Monod discovered that bacteria group the genes that encode the proteins for a certain metabolic pathway in a single transcription unit (which they called ‘operon’). They won the Nobel Prize in Physiology or Medicine in 1965 for their discovery.
The bacteria they chose for their study was Escherichia coli, which normally lives in the intestines of healthy people; specifically, they studied the set of genes E. coli bacteria need to transport lactose (milk sugar) and break it down. E. coli only produces the three proteins it needs to digest lactose when the sugar is available. To simplify transcription regulation, the three genes involved are adjacent in the genome and under a single regulation system. Similar transcriptional regulation systems are found in other metabolic pathways in all bacteria.
Research at Navarrabiomed
In 2018, the team of researchers at Navarrabiomed coordinated by Iñigo Lasa Uzcudun, Head of the Microbial Pathogenesis Unit and Director of the biomedical research centre, described a new way genes are organised in bacteria. This regulation system has a higher level of regulation in operon structure, which the authors of the study named ‘non-contiguous operon’.
The bacterial model analysed has a group of four genes that are transcribed as a transcription unit despite the existence of a separate gene between the second and third genes that is transcribed in the opposite direction.
This transcriptional architecture results in an antisense transcript that acts as a mutual regulation system for the expression of the genes in the operon and the gene that produces this antisense transcript. Therefore, the concept of non-contiguous operon includes not only the genes transcribed from the same transcription unit but also overlapping genes whose expression is coordinated with that of the genes in the operon.
This finding deepens the understanding of bacterial biology and may trigger novel developments in the fields of synthetic biology and bacterial biotechnology.
The study was carried out as part of the scientific activity done at the Navarra Medical Research Institute (IdiSNA).
Un equipo científico del centro de investigación biomédica Navarrabiomed -centro mixto del Gobierno de Navarra y la Universidad Pública de Navarra (UPNA)- ha conseguido caracterizar el sistema sensorial que las bacterias utilizan entre otras cosas para multiplicarse en el cuerpo humano y causar infección.
El avance, que ha sido publicado por la revista científica Nature Communications y cuenta con financiación del Ministerio de Economía, Industria y Competitividad, permite comprender mejor cómo las bacterias se adaptan a las diferentes condiciones ambientales y posibilitará el desarrollo de antibióticos más específicos y eficaces.
El estudio ha contado con el liderazgo del doctor Iñigo Lasa, director de Navarrabiomed e investigador responsable del Grupo de Patogénesis Microbiana del centro. Asimismo, han colaborado investigadores del Instituto de Agrobiotecnología (UPNA-CSIC-Gobierno de Navarra), del Instituto de Biomedicina de Valencia (CSIC) y del Institute of Infection, Immunity and Inflammation, University of Glasgow.
Bacterias superresistentes
Actualmente, la aparición de bacterias farmacorresistentes, que no responden a tratamientos con antibióticos, constituye uno de los problemas sanitarios a escala mundial priorizados por la Organización Mundial de la Salud (OMS).
Las bacterias detectan, responden y se adaptan a los cambios en su entorno utilizando unos elementos sensoriales denominados sistemas de dos componentes. Este tipo de sistemas sensoriales están presentes en bacterias, hongos y plantas, pero no se encuentran en células animales. En el caso de las bacterias, regulan procesos celulares tan importantes como la virulencia o su propio crecimiento, lo que los convierte en dianas para el diseño de nuevas terapias antimicrobianas.
El objetivo del trabajo ha consistido en eliminar todos los sistemas de dos componentes, es decir el sistema sensorial completo, en Staphylococcus aureus, uno de los principales patógenos humanos según la OMS y, posteriormente, en la generación de una colección de bacterias cada una de las cuales contiene un único sistema de dos-componentes. Esta estrategia ha permitido simplificar una compleja red sensorial en cada uno de sus elementos para comprender cuál es la función individual de cada uno de los sistemas y la relación existente entre ellos.
Aplicación clínica de la investigación
En relación a la aplicación clínica, Iñigo Lasa apunta al desarrollo de nuevos antibióticos más específicos. “El hecho de que los sistemas de dos componentes estén presentes en todas las bacterias patógenas y no en las células de nuestro organismo nos puede permitir desarrollar fármacos que bloqueen estos sistemas, evitando así el desarrollo de la bacteria durante la infección, sin causar ningún efecto secundario sobre nuestras células”.
En este sentido, las bacterias generadas en este estudio han sido patentadas y actualmente el equipo analiza diversos compuestos marinos que puedan incorporarse en el tratamiento y control de infecciones en la práctica clínica.
La investigación forma parte de la actividad científica del Instituto de Investigación Sanitaria de Navarra (IdiSNA), agrupación público-privada para el fomento de la investigación biomédica en la Comunidad Foral y de la que son miembros Navarrabiomed y la UPNA.
Navarrabiomed - Centro de investigación biomédica
Complejo Hospitalario de Navarra, edificio de investigación.
Calle Irunlarrea, 3. 31008 Pamplona, Navarra, España.