Research topics in Slovenia related to PathoGenoMics

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Research topics in Slovenia related to
PathoGenoMics

• Dr. Livija Tuar
• Ministry of Higher Education, Science and
  Technology
• Dr. Roman Jerala
• National Institute of Chemistry
• Bonn, 7.8. April 2005

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Resarch activity financing related to
PathoGenoMics

• Research programms (5 years)
• 13 programms from 2004-2008
• In year 2004 the budget was 2.9 MEUR
• Basic and applied research projects (2-3 years)
• 15 projects financed from 2004 (0.3 MEUR/2004)
• Young researchers (up to 4 years)
• 22 young researchers financed in 2004 (0.4 MEUR)
• Research infrastructure
• 0.46 MEUR for research instruments in 2004
• International cooperation
• 5 bilateral projects 2004/2005 (travel,
  subsistence costs)
• Participation in 5th and 6th FW projects

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Main areas of research of participating groups

• Microbiology
• Immunology
• Biochemistry and molecular biology
• Genetics
• Veterinary medicine
• Pharmacy

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Affiliation of participating groups

• University of Ljubljana
• medical faculty
• biotechnical faculty
• University of Maribor
• medical faculty
• National institute of chemistry

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• Research Program
• Coexsistence of parasites
• Prof. Dr. Tatjana Avsic Zupanc,
  avsic_at_mf.uni-lj.si
• Development and introduction of quick diagnostic
  methods for discrimination of bacterial and
  fungal infections
• Study of emerging microogranisms in the area of
  Slovenia, establishment of the best possible
  methodology for their discovery
• Study of natural resistance and immune response
  of host defence against microorganisms.
  (Examination of apoptosis, clonal selection,
  cytokine dependent poliferation and
  differentiation of cells of the immune system.
  Importance of cytokines in regulation of immune
  system.)
• Study of immunopathologic changes in inflammatory
  tissue and testing of mechanisms of invasion and
  defence on animal models
• Study of ecology and epidemiology of some
  microorganisms important for Slovenian territory.
  Investigation on genetic markers significant to
  host-carrier-parasite relationship.
• Study of improvements in diagnostic procedures,
  genetic variability and spread of Hepatitis C in
  Slovenia

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• Research Program
• Coexsistence of parasites
• Prof.Dr. Tatjana Avsic Zupanc, avsic_at_mf.uni-lj.si
• Microorganisms studied
• -Bacteria Staphylococcus aureus, Streptococcus
  pyogenes, Streptococcus pneumoniae, Listeria
  monocytogenes, Escherichia, Pseudomonas,
  Haemophilus influenzae, Helicobacter pylori,
  Borrelia burgdorferi
• -Eucariotic organisms Toxoplasma sp.,
  Cryptosporidium parvum, Blastocystis hominis,
  Diroflaria repens, Dermatobia homini
• -Viruses Caliciviruses, herpes virus 6, tick
  borne meningoencephalitis, hepatitis B, C,
  cytomegalovirus

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• Research Program
• Comparative genomics and genome biodiversity
• Prof.Dr. Peter Dovc, peter.dovc_at_bfro.uni-lj.si
• Study of immune response to natural and
  experimental infections in animal models signal
  pathway for triggering the immune response,
• Identification of abnormalities in the genome
  with cytogenetic molecular methods and
  bioinformatic approach with the goal to establish
  novel diagnostic methods, identification of
  mutations, which affect reproductive performance,
  
• Microorganisms studied
• -Mycoplasma spec., Chlamydia spec....

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• Research Program
• Biology of microorganisms
• Prof.Dr. Miklavz Grabnar, miklavz.grabnar_at_uni-lj.s
  i
• Study of microbial virulence factors expression
  of colicins and biotechnological production for
  therapeutic purposes, regulation of virulence
  determinants in a population of bacterial cells,
• Study of bacterial resistance mechanisms to
  antimicrobial compounds resistance against the
  peptide antibiotic bacitracin
• Microorganisms studied
• -Bacteria Bacillus spec., Clostridium spec,
  Escherichia spec, Klebsiella spec.

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• Research Program
• Molecular biology from the dynamics of
  biological systems to applications
• Prof.Dr. Roman Jerala, roman.jerala_at_ki.si
• Molecular basis of the recognition of pathogen
  associated molecular patterns by Toll-like
  receptors
• Structure-based design of antimicrobial agents
  (peptides) which neutralize endotoxin
  Identification of structural motif for efficient
  neutralization of endotoxin by small peptides
• Microorganisms studied
• -Gram-negative bacteria Escherichia coli,
  Pseudomonas aeruginosa, Brucella abortus,
  Helicobacter pylori
• -Gram-positive bacteria Staphilococcus aureus,
  Staphylococcus epidermidis,
• -Fungi Aspergillus niger

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• Research Program
• Pharmaceutical chemistry designing, synthesys
  and analysis of drugs
• Prof.Dr. Danijel Kikelj, danijel.kikelj_at_ffa.uni-lj
  .si
• Rational design, synthesis, characterization and
  biological testing of new active compounds of
  pure synthetic or natural origin peptidomimetics
  (e.g. thrombin inhibitors, fibrinogen receptor
  antagonists, analogs of N-acetylmuramyl-L-alanine-
  D-isoglutamine)
• Investigation of new diagnostic markers for
  specific detection, diagnosis and monitoring of
  different pathological states.

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• Research Program
• Microbiology and biotechnology of food and
  environment
• Prof.Dr. Peter Raspor, peter.raspor_at_bf.uni-lj.si
• Study of the effect of biological factors and
  their interactions, physical and chemical stress
  parameters on microorganisms in laboratory model
  systems nutrients supply, temperature, humidity,
  concentrations of salts, metal ions and different
  anti-microbial agents...,
• Study of the ecology of microbial populations and
  communities in complex model and natural systems
  (soil, water) and bioprocess environments
  (grapes/must and other foods anti-microbial
  agents production),
• Development of classical and molecular-biological
  methods for detection, identification and
  tipization of microorganisms in food and
  environment for detection and monitoring of
  microorganisms in natural and industrial
  environments.
• Microorganisms studied
• -Bacteria Listeria monocytogenes, Bacillus sp.,
  Shigella sp., Vibrio cholerae, Campylobacter
  jejuni, Acetobacter sp., Lactobacillus sp., ...
• -Fungi Yeasts Saccharomyces sp, Candida sp....

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• Research Program
• Nutrition and ecology of gastrointestinal tract
• Dr. Irena Rogelj, irena.rogelj_at_bfro.uni-lj.si
• Study of interactions of microorganisms in the
  human and/or animal gastrointestinal tract
  ecosystems using in vitro, ex vivo and in vivo
  methods and animal models,
• Nutrition studies in domestic and laboratory
  animals monitoring of metabolic parameters and
  investigation of nutritional factors by different
  biological markers, microbial activity in
  particular parts of the intestinal tract...,
• Study of mechanisms and new approaches in
  feeding, enabling the production of functional
  food of animal origin, finding out the effects of
  selected probiotics and prebiotics on the
  composition of microbial population in the gut of
  domestic animals or humans...
• Selection of markers for measurement of
  influences of feed, nutrients, probiotics and
  other bioactive substances in organism and
  development of toxicological, genotoxicological
  and immunological methods for tracing of their
  positive and negative effects.
• Microorganisms studied
• -Bacteria Lactobacillus sp....

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• Research Program
• Diseases in Slovenia caused by arthropods
• Prof.Dr. Franc Strle, franc.strle_at_mf.uni-lj.si
• Antigenic and genetic characterization of
  tick-borne diseases Lyme boreliosis, Human
  granulocytic ehrlichiosis (HGE) and
  meningoecephalitis,
• Development of diagnostic techniques for
  tick-borne diseases detection
• Microorganisms studied
• -Bacteria Borrelia burgdorferi, Rickettsia sp.
• -Virus tick borne meningoencephalitis

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• Topics of research proposals from Slovenia
  regarding to Pathogenomics proposed research
  agenda
• A The microbes (1)
• Screening of epithelial cells for probiotic
  bacteria
• B Host-microbe interractions (6)
• Host recognition of pathogenic microorganisms
• Screening of epithelial cells for probiotic
  bacteria
• Invasive growth mechanisms and diagnostical
  methods
• New methods for detection, prediction and
  antimicrobial treatment of pathogens on
  ephitelial cells
• Inhibitors of microbial growth in food
• Emerging risk zoonosis control
• C Development and improvement of tools (7)
• Development of novel principles for
  anti-microbial treatment for replacing or
  supplementing anti-microbial treatment
• Host recognition of pathogenic microorganisms
• Cytokines as adjuvants and bioassays for immune
  response
• Development of new diagnostical tools for
  autoimmune diseases
• Invasive growth mechanisms and diagnostical
  methods

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Proposed future research topics in PathoGenoMics

• 1. Development of novel principles for
  anti-microbial treatment for replacing or
  supplementing anti-microbial treatments
• 2. Host recognition of pathogenic microorganisms
• 3. Cytokines as adjuvants and bioassays for
  immune response
• 4. Screening of epithelial cells for probiotic
  bacteria
• 5. New methods for detection, prediction and
  antimicrobial treatment of pathogens on
  ephitelial cells

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Proposed future research topics in PathoGenoMics

• 6. Development of new diagnostical tools for
  autoimmune diseases
• 7. Invasive growth mechanisms and diagnostical
  methods
• 8. Inhibitors of microbial growth in food
• 9. Emerging risk zoonosis control
• 10. Diagnostical tools for transfer of virulence
  factors

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• 1. Development of novel principles for
  anti-microbial treatment for replacing or
  supplementing current anti-microbial treatment.
• Novel therapeutic priciples to overcome
  resistance to current antimicrobials. Innovative
  approaches to exploit knowledge of host/pathogen
  interactions and microbial and host genome for
  the development of new anti-bacterial and/or
  antifungal treatment and/or prophilaxis against
  micro-organisms resistant to existing
  antimicrobials.
• 2. Host recognition of pathogenic microorganisms.
  
• Molecular mechanism of recognition of pathogenic
  microbes, microbial strategies to evade detection
  by the host, identification of potential targets
  for therapeutic intervention, potential for
  development of novel targets or therapies to
  boost immune response or prevent excessive
  stimulation. Genetic susceptibility to microbial
  infection, correlation to atherosclerosis or
  autoimmune diseases, identification of risk
  factors.

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• 3. Cytokines as adjuvants and bioassays for
  immune response
• Development of alternative strategies to manage
  infectious diseases in animals by development
  and application of new vaccines, based on
  alternative adjuvants providing long-term and
  safe protection, without side-effects. Use of
  innovative approaches exploiting knowledge on
  cytokines to study the immune response during
  vaccination. The development of use of different
  cytokines as vaccine as well as probiotics
  adjuvants is encouraged.
• Development of different types of biological
  assays for interferons based on antiinvasive,
  immunomodulatory, antiproliferative, antitumor
  activity.
• Particularly encouraged is the development of
  different new cell systems specifically sensitive
  to such kind of biological activities in
  comparison to ELISA.

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• 4. Screening of epithelial cells for probiotic
  bacteria
• Research on the probiotic microbial flora
  composition in the intestinal tract. Studies on
  the bacterial adhesion mechanisms on the
  epithelial cells of the intestinuum. The
  isolation and cultivation of intestinal
  epithelial cells of different animal species,
  such chicken, pig, bovine, human as well as their
  screening for probiotic bacteria in vitro should
  be included into the research.
• 5. New methods for detection, prediction and
  antimicrobial treatment of pathogens of
  ephitelial cells.
• Development of molecular biology based methods
  for detection and prediction of the occurrence
  and virulence of pathogens and host-pathogen
  interaction. Development of principles and
  methods that can reduce the viability and
  virulence/infectivity of pathogens on epithelial
  cells. Innovative approach to exploit knowledge
  of cross-talk between pathogen-epithelium-immune
  system in cell functional models.

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• 6. Development of new diagnostical tools for
  autoimmune diseases
• Microbial antigenes have the potential to
  initiate autoreactivity through molecular
  mimicry, polyclonal activation, or the release of
  previously sequestered antigens.
• Development of innovative approaches, exploiting
  knowledge of different DC subsets in peripheral
  blood and development of in vitro system is
  proposed. Innovative approaches, exploiting
  knowledge of peripheral B-lymphocyte
  subpopulations in infections with such organisms
  and in patients with autoimmune diseases (SLE).
  Development of diagnostically valuable tools for
  monitoring progress of disease in patients with
  SLE.

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• 7. Invasive growth mechanisms and diagnostical
  methods
• The problem of new food borne pathogenes in
  immunocompromised human population. Understanding
  mechanisms of invasive growth of pathogen
  microorganisms. Development of methods (in vitro,
  in vivo) and determination of parameters for
  invasive growth monitoring is encouraged.
• 8. Inhibitors of microbial growth in food
• Screening of new pathogen microbial growth
  inhibitors in traditional food matrices.
  Development of (in vitro, in vivo) methods to
  study mechanisms of inhibition of pathogen
  microorganism growth in host (gastrointestinal
  tract).

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• 9. Emerging risk zoonosis control
• Regulation mechanisms of host invasion of
  pathogenic microorganisms representing major
  emerging risk zoonosis viable but not culturable
  microorganisms Campylobacter sp., Mycobacterium
  paratuberculosis.
• Development of early warning diagnostic tools for
  microorganisms in animals and human capable to
  switch-on pathogen activity based on the
  knowledge of virulence genetic information.
  Determination of selective molecular markers.
• 10. Diagnostical tools for transfer of virulence
  factors
• Development of early warning systems diagnostic
  tools for microorganisms in animals and human
  capable of intra (inter) species transfer of
  virulence factors based on the genetic
  information of virulence transfer mechanisms.