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Research
interests and Projects |
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1. Research interests |
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The Prokaryotic Development Group (BIO318),
that has the honor of holding the “University of Granada for Excellent
Research Award", performs research with the multicellular bacterium Myxococcus xanthus combining classical microbiology,
molecular biology and microscopy techniques, with massive sequencing,
transcriptomic, bioinformatics, and comparative genomics technologies. Our main interest is to discover the molecular
mechanisms involved in the M. xanthus multifaceted social behaviors that maximize
the use of resources and its survival by adopting a multicellular lifestyle,
in a way that resembles to eukaryotic organisms. Furthermore, we also perform research about the global molecular
response of bacteria to the different changes that they face in the
environment, such as the presence of copper and other metals. We are also
interested in deciphering the extraordinary predatory capacity of M. xanthus. This
bacterium secretes a plethora of secondary metabolites to kill prey, but many
of them remain silenced under laboratory conditions. Interactions between
microorganisms may increase the production of these secondary metabolites
leading to the discovery of new metabolic compounds, so the co-culture
predator-prey should be considered as a new biotechnological approach in the
current antibiotic crisis era. For these reasons, the World Health
Organization has proposed in a recent report “reorientating
research to better understand the role of bacteria and their ecological
relationships” as a guideline to effectively deal with antibiotic
resistance to avoid drifting back to a pre-antibiotic era. We are using
"omic" technologies to decipher the
interaction of M. xanthus
with other soil bacteria such as Streptomyces
or Sinorhizobium meliloti to
try the awakening of silenced genes. We
are also studying the role of iron
and siderophores in predation and the impact of predation of the symbiosis
rhizobium-leguminous plants. We have participated in more than 30 competitive
research projects, including 11 National projects, 2 projects with companies,
1 FEDER project, 1 Project for Excellence Research from Junta de Andalucía, 1
CONSOLIDER-INGENIO, 1 COST ACTION, 1 Granada
Research of Excellence Iniciative on Biohealth (GREIB), several Interchange
projects and several Integrated Actions. We have organized the “1ª Reunión
Científica de la Red Nacional de Genómica Bacteriana”, the “34th
International Conference on the Biology of Myxobacteria”
and two International Workshops. The formative capability of the group is
extensive. We have supervised 9 doctoral thesis, more than 30 master thesis
and more than 35 experimental final degree projects. The group has published in prestigious
scientific journals such as Nature of Biotechnology, Cell, Proceedings of the
National Academy of Science, Nucleic Acids Research, Annual
Review on Microbiology, Computational and Structural Biotechnology Journal, PLos Genetics, Environmental Microbiology, Journal of
Biological Chemistry, Frontiers in Microbiology, Molecular Microbiology, etc. Myxobacteria: models of prokaryotics
multicellularity and bacterial predation Myxobacteria (Myxococcota Phylum) exhibit a peculiar
multicellular cell cycle: |
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The complex signal transduction in myxobacteria |
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Completion of the multicellular process
requires a controlled cell-cell interaction. M. xanthus possess three main types of signal
transduction systems: two component systems, extracytoplasmic
function sigma factors (ECF) and Serine/Threonine protein kinases (STPK). Our
group is interested in the study of signal transduction mechanisms during
development by using functional classic molecular biology, genomic and
transcriptomic approaches. |
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Deciphering of M. xanthus global response to copper |
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M. xanthus
is a soil bacterium and therefore it has to complete its life cycle in the
presence of soil natural compounds.
One of these compounds is copper, which is present in soils to
concentrations that fluctuate between 2-100 mg/Kg. This metal is essential
for life because it is used as cofactor by many enzymes involved in vital processes.
However, copper is also extremely toxic mainly through the formation of
reactive oxygen species. Due to this dual effect, cells have different
mechanisms to ensure appropriate intracellular copper levels. M. xanthus
give us the opportunity to study cell global response during a complete life
cycle. This research, that is being performed using classic molecular biology
and functional genomic techniques, has allowed to describe a new group of
metal dependent ECF sigma factors. |
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Copper induces carotenoids in M. xanthus (Moraleda_Muñoz
et al., 2005) |
M. xanthus global copper response
(Pérez et al., 2018) |
Mechanism of action of a new group of CorE-like metal dependent ECF
sigma factors (Gómez-Santos et al., 2011; Marcos-Torres et al., 2106) |
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The largest known bacterial genomes |
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Several
sequenced myxobacterial strains possess genomes
among the largest ones described in prokaryotes, making them excellent models
for the study of genome expansion. The expansion of myxobacterial genomes is
mainly due to gene duplication and divergence. Our group is studying the evolution
of several families of paralogs. |
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Expansion of Serine/Threonine protein kinases in the myxobacteria
genomes (Pérez et al., 2008) |
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Bacterial predation: basic studies, and ecological, evolutionary,
biotechnological and agricultural consequences Bacterial
predation has been proposed as an evolutionary driving force. The structure
and diversity of the predatory bacterial community is beginning to be
recognized as an important factor in biodiversity due to its potential role
in controlling and modelling bacterial populations in the enviroment. M. xanthus is a soil bacteria that is
able to prey on a variety of other bacteria as well as fungi. We are studying
the strategies of M. xanthus predation
on other important soil bacteria such as Streptomyces
or Shinorhizobium. The predatosome
(M. xanthus genes involved in
predation) and defensome (S. meliloti
genes involved in the defense of the prey) are being studied by using massive
sequecing (RNA seq), genomic and classical molecular biology and microbiology
techniques. The research will shed light on the unknown killing processes
used by these small predators. Since these bacteria have the genetic
potential to produce a large battery of antibiotics, in vivo studies against
prey, will help to discover new products with biological activity and may
open new horizons in their application in biocontrol processes against
pathogenic bacteria, as an alternative to antibiotics. On the other hand, the
defense mechanisms of the prey will help us to unveil new strategies of
bacteria against antibiotics. |
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M. xanthus versus S. versicolor (Pérez
et al., 2016) |
M. xanthus
versus
different strains of S. meliloti (Muñoz-Dorado
et al., 2014) |
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Defense mechanisms in the prey with biotechnological
applications (Pérez et al., 2020) A.
Silenced antibiotics are induced in the prey during the predatory process. In
the pictures, M xanthus (Mx, predator) induces in Streptomyces coelicolor (Sc, prey) the blue antibiotic
actinorhodin, in solid and liquid media. B. Novel
antibiotic resistance mechanisms have been discovered in Bacillus thuringensis: myxovirescin TA glucosylation. C. Other physical/chemical defenses
mechanisms induced by M. xanthus
predation in different bacteria. Galactoglucan (left picture) and melanin
(middle picture) protect S. meliloti
from predation. M. xanthus induces
development in Streptomyces (right
picture). Pictures from panel A and right picture from panel Care reproduced
from Pérez et al. (2011). Left picture in panel C is adapted from
Muñoz-Dorado et al., (2016). Middle picture in panel C is from
Contreras-Moreno et al. (2020). |
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Transcriptome
dynamics of the Myxococcus
xanthus
multicellular
developmental program (Muñoz-Dorado et al., 2019)
The relative expression
profiles of M. xanthus genes
observed during the
developmental program. Ten
Developmental Groups (DGs).
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Iron uptake are induced during predation
(Pérez et al., 2022)
A. Genes predicted to be involved in iron
uptake and that are upregulated in co-culture at t2 and/or t6. The numbers of
the genes depicted in the figure are the corresponding MXAN_
identifiers.
B. Graphical
representation of the cluster of genes involved in myxochelin
biosynthesis. The seven upregulated transcripts are indicated by their
corresponding gene name.
C.
Fur box (FB) predicted by using the Virtual Footprint database. Red balls: Fe3+; blue balls: Fe2+. OM, outer membrane; IM, inner membrane.
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2. Research
Projects 2.1. Research Funded
Projects • Unravelling the potential of LysM-domain proteins to awaken silent secondary
metabolites genes in predatory bacteria through predator-prey interactions.
LYSM. HORIZON.1.2 - Marie Skłodowska-Curie
Actions (MSCA). https://cordis.europa.eu/project/id/101106411.
Grant agreement
ID: 101106411. Investigador principal: Francisco Javier Marcos Torres. • Bacterias
depredadoras: nuevas estrategias en la crisis de los antibióticos. 2021-2023.
Proyectos Frontera. FEDER. ANDALUCIA. A‐BIO‐126‐UGR20. Investigadores principales: Juana Pérez Torres y
Aurelio Moraleda Muñoz. • Estudios
sobre depredación bacteriana y su impacto en agricultura. 2021-2024. MCI.
Proyectos de I+D+i en el marco de los programas
estatales de generación de conocimiento y fortalecimiento científico y
tecnológico del sistema de I+D+i.
PID2020-112634GB-I00. Investigadores principales: Aurelio Moraleda Muñoz y
José Muñoz Dorado. • Depredación
bacteriana: estudio del predatosoma de Myxococcus xanthus y
el defensoma de Sinorhizobium meliloti.
2016-2020. MEC. BFU2016-75425-P
(Programa estatal de fomento de la investigación científica y técnica de
excelencia, Subprograma estatal de generación de conocimiento).
Investigadores principales: Aurelio Moraleda Muñoz y José Muñoz Dorado. • Red de
Excelencia. Microgen-NET. 2017-2018. Ministerio de
Economía y Competitividad: Acciones de Dinamización. Ref. Consolider
CGL2015-71523-REDC. Coordinador:
Francisco Rodríguez Valera, Investigador responsable de la Universidad de
Granada: José Muñoz Dorado. • Estudios
sobre rutas de transducción de señales mediadas por proteínas quinasas de
tipo eucariota durante el desarrollo. 2013-2015. MEC. Ref. BFU2012-33248.
Investigador principal: José Muñoz Dorado. • MICROBIAL
COMPARATIVE GENOMICS. 2009-2014. MCyT:
CONSOLIDER-INGENIO 2010. Ref. CSD2009-00006 Coordinador: Francisco Rodríguez
Valera, Investigador responsable de la Universidad de Granada: José Muñoz
Dorado. • Las quinasas
de Myxococcus xanthus
como modelo de evolución de parálogos. 2010- 2012. MCyT. Ref. BFU2009-07565 (Subprograma BMC)."
Investigador principal: José Muñoz Dorado. • Respuesta
global al cobre en Myxococcus xanthus.
2007-2010. Proyecto Excelencia Junta de Andalucía. Ref. CVI1377. Investigador
principal: José Muñoz Dorado. • Acción
integrada entre la Universidad de Granada y Universidad de Georgia.
2009-2010. PLAN PROPIO UNIVERSIDAD GRANADA. Investigador principal: José
Muñoz Dorado. • Oxidasas multicobre de Myxococcus xanthus: regulación y función durante el crecimiento
vegetativo y el ciclo de desarrollo. 2006-2009.
MEC. Ref. BFU2006-00972/BMC. Investigador
principal: José Muñoz Dorado. • Expression, purification and structural
characterization of a multicopper oxidase of Myxococcus xanthus. 2006-2007.
MEC. Acción integrada Hispano Portuguesa. MEC. Ref:
HP2005-0034. Coordinadores: José Muñoz Dorado y Ligia O. Martins. • RED NACIONAL
DE GENÓMICA BACTERIANA. 2004-2007. Genoma España y MEC. Coordinadores:
Fernando Rojo (Centro Nacional de Biotecnología, Madrid) y Alex Mira Obrador
(Universidad Miguel Hernández). • Estudios
sobre las rutas de transducción de señales en las que intervienen proteínas
quinasas y fosfatasas de tipo eucariótico en
Myxococcus xanthus.
2003-2006. MCYT. Ref:
BMC2003-02038. Investigador principal: José Muñoz Dorado. • Búsqueda de
los elementos corriente arriba y abajo de los sistemas reguladores de dos
componentes PhoR1-PhoP1, PhoR2-PhoP2 y PhoR3-PhoP3 de Myxococcus xanthus. 2000-2003. Dirección General
de Enseñanza Superior e Investigación Técnica. Ref:
BMC2002-03012. Investigador principal: José Muñoz Dorado. • RED TEMÁTICA del programa de Biotecnología:
"Biodegradacion de lignina y hemicelulosa. Aspectos enzimáticos, químicos y
moleculares, y sus aplicaciones industriales y medioambientales". MCyT.Refs: BIO95-1057-E, CICYT-BIO98-1841-E; CICYT2002,
BIO2004-20903-E, Bio2009-07866-E, BIO2011-15394-E. 1993-2014.Coordinador:
Susana Camarero Fernández (Centro de Investigaciones Biológicas, Madrid,
CSIC). 2.2. Research Competitives Grants • Predoctoral
contract. FEDER. Andalucia. Francisco
Javier Contreras Moreno (15/06/2022-15/06/2023). Investigador responsable:
Juana Pérez Torres • Predoctoral contract. Junta de
Andalucía. Programa de empleo juvenil. Fondo Social Europeo. Subprograma
Joven investigador. Lucía Cabello Alemán (06/14/2021-21/05/2021).
Investigador responsable: Aurelio Moraleda Muñoz. • Predoctoral contract. Junta de
Andalucía. Programa de empleo juvenil. Fondo Social Europeo. Subprograma
Joven investigador. Ana Alberola Romano
(06/04/2021-21/05/2021). Investigador responsable: Aurelio Moraleda
Muñoz. • Predoctoral
contract University of Granada from the research project BFU2016-75425-P. 31/07/2019
-29/12/2019. Francisco Javier Contreras Moreno. Investigador responsable:
Aurelio Moraleda Muñoz. • Predoctoral contract. Junta de
Andalucía. Programa de empleo juvenil. Fondo Social Europeo. Subprograma
Joven investigador. 31/01/2018- 30/07/2019. Francisco Javier Contreras Moreno.
Investigador responsable: Aurelio Moraleda Muñoz. • Senior mobility grant Salvador de
Madariaga. Ministerio de Educación. Juana Pérez Torres.
01/03/2018-30/06/2018. • Senior mobility grant Salvador de
Madariaga. Ministerio de Educación. José Muñoz Dorado. 01/03/2018-30/06/2018. • Predoctoral contract.
Junta de Andalucía. Programa de empleo
juvenil. Fondo Social Europeo. Subprograma Contratos de personal técnico.
31/10/2017- 03/06/2018. María del Carmen Rodríguez López. Investigador
responsable: Aurelio Moraleda Muñoz. • Predoctoral contract. Junta de
Andalucía. Programa de empleo juvenil. Fondo Social Europeo. Subprograma
Contratos de personal técnico. 01/06/2017-26/10/2018. Natalia Isabel Garcia Tomsing. Investigador
responsable: Aurelio Moraleda Muñoz. |
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