ProCel - Bases Moleculares de la Proliferación Celular - Dept. Biología Molecular y Bioquímica
Universidad de Málaga
Amine system project
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METABOLIC SYSTEMS

ACTIVIDAD INVESTIGADORA

Amino acid metabolism plays en essential role in the homeostasis of any living organism. In the past, these pathways have been studied as independent biochemical elements. Nevertheless, they take part of an extremely complex network [Expasy Metabolic Pathway], regulated by complex mechanisms that cannot be fully characterized by the simple sum of the characteristics of its elements, but from the discovery of the emergent properties of the network. In mammals, this network play important role in the physiologic pH control (arginine metabolism), in tumor proliferation and its consequences on the host caquexia (Gln, Asn and polyamines), neurotransmission (Glu, and amines derived from cationic and aromatic amino acids), immune responses and inflammation (histamine, NO), and in the multiple metabolic reactions involving methylation, as polyamine and sterol biosynthesis and gene expression (S-adenosyl methionine and methyl cycles).

Our group has 20-year background in the study of amino acid metabolism and its roles in physiopathological processes as cancer, immune response, and different rare genetic diseases (click here to see representative publications). In the last 6 years, we tried to approach these problems by using Systems Biology strategies, including the combination of “in silico and “omics” technologies. Our hypothesis is that new emergent properties can be revealed by integration of the known information about the elements plus an iterative process of modeling and experimental validation and refinement. We apply different predictive techniques: molecular modeling and molecular dynamics simulations, predicting protein function, metabolic modeling and topologic analysis of biological networks (see figure). Many different experimental approaches are currently used to contrast our predictions/models. They included Biophysics-based technologies, Enzymology, Metabolic Analysis, Immunological and recombinant DNA-techniques (including direct mutagenesis, cell transfection, etc), as well as new HTP-technologies (expression arrays and proteomics).

Figura1

Our general aims are:

  • To gain new basic knowledge on the regulatory properties of the network.
  • To apply this knowledge to find more specific and/or sensible new targets for diagnosis, prognosis and/or treatment of the different pathologies related to the metabolic pathways.

According to these hypothesis and strategies, we have developed and are engaged in the following Projects and International Networks.




GRANTS AND COOPERATIVE NETWORKS FOR THE PAST 5 YEARS:

Grant Títle: Hacia una visión integradora del metabolismo en células de mamíferos: Aplicaciones en enfermedades raras y emergentes.
Funded by (Grant code): Ministerio de Economía y Competitividad (SAF2011-26518).
Participants (Institutions): UMA y Univ. Eastern Finland
Principal Investigator: Sánchez Jiménez F.

Grant Títle: Análisis del efecto de chaperonas farmacológicas sobre proteinas mutantes en la enfermedad de Gaucher.
Funded by (Grant code): CIBER de Enfermedades Raras. Instituto de Salud Carlos III (Ministerio de Sanidad y Consumo).
Participants (Institutions): CIBER-ER, UMA y Hospital Universitario Miguel Servet
Principal Investigator: Giraldo P.

Grant Títle: Network of excellence: systems microscopy- a key enabling methodology for next-generation systems biology.
Funded by (Grant code): UE. FP7-HEALTH-2010-258068.
Investigador responsable(en la UMA): García-Ranea JA

Grant Títle: Una propuesta de la Biología de Sistemas para el estudio transversal de enfermedades raras y emergentes.
Entidad Financiadora: Plan Andaluz de Investigación, Desarrollo e Innovación (Proyecto de Excelencia 2010).
Principal Investigator: Sánchez Jiménez F.

Grant Títle: Predicción y modelado de redes de proteínas aplicado al estudio de enfermedades raras en humanos y su tratamiento.
Funded by (Grant code): Ministerio de Ciencia e Innovación (MICINN). SAF2009-09839
Participants (Institutions): CIBER-ER y University College London
Date, from: 2010 up to: Hoy
Participants (Institutions): CIBER-ER y la University College London
Principal Investigator: García-Ranea JA

Grant Títle: Recent advances in histamine receptors H4R research.
Funded by (Grant code): COST Action BM0806
Participants (Institutions): 7 paises de la UE
Date, from: 2009 up to: 2012
Principal Investigator: Sánchez-Jiménez F
Número de investigadores que apoyaban la petición: 7

Grant Títle: Avances hacia una visión sistémica del metabolismo de aminoácidos catiónicos en células de mamíferos. Aplicaciones en Biomedicina.
Funded by (Grant code): Ministerio de Ciencia e Innovación (MICINN). SAF2008-02522
Participants (Institutions): UMA
Date, from: 2009 up to: 2011
Principal Investigator: Sánchez-Jiménez F
Número de investigadores que apoyaban la petición: 8

Grant Títle: Caracterización Estructural y funcional del transportador de hormona tiroidea MCT8.
Funded by (Grant code): CIBER de Enfermedades Raras. Instituto de Salud Carlos III (Ministerio de Sanidad y Consumo)
Date, from: 2009 up to: hoy
Principal Investigator: Sánchez-Jiménez F
Número de investigadores que apoyaban la petición: >7

Grant Títle: Desarrollo y Aplicación de Estrategias Biocomputacionales para la caracterización de las bases moleculares de enfermedades metabólicas hereditarias.
Funded by (Grant code): CIBER de Enfermedades Raras. Instituto de Salud Carlos III (Ministerio de Sanidad y Consumo)
Date, from: 2009 up to: hoy
Principal Investigator: Sánchez-Jiménez F
Número de investigadores que apoyaban la petición: >7

Grant Títle: Integración y modelado del metabolismo y efectos biológicos de las aminas biógenas, biomoléculas directamente implicadas en enfermedades raras y emergentes.
Funded by (Grant code): Fundación Ramón Areces
Participants (Institutions): UMA
Date, from: 2007 up to: 2010
Principal Investigator: Miguel Ángel Medina
Número de investigadores participantes: 9

Representative publications of the trajectory of the group (prior to 2005).




LINKS AND COLLABORATIONS:

CIBER-ER - KHAOS - UCL - COST - CSIC - REMA - ICIII - MICINN - UMA - PAI

Molecular Basis of Cell proliferation. Departament of Melecular Biology and Biochemistry. University of Malaga Campus de Teatinos s/n 29071 MÁLAGA. Teléfono: (+34) 952 13 71 35. Fax: (+34) 952 13 16 74 - 20 00.
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