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Evolution and variation  In vivo infection biology  Development of techniques   Difficult microbes  Bacteriophages   Host-microbe interactions   Diagnostics     Probiotics   P   0` 33` Sf3f` 33g` f` www3PP` ZXdbmo` \ғ3y`Ӣ` 3f3ff` 3f3FKf` hk]wwwfܹ` ff>>\`Y{ff` R>&- {p_/̴>?" dU$z? " dZ  @" `  n?" dZ(   @@``PR    @ ` ` p>  >   c(     `o jJ jJ1 ?"@ ~ o 9Title ZB  c $?" ZB  c $?"` ZB  c $)?"*$$ X  C "A logo"2l  6A)?" M^:  0o "S>-~  o <Mikael Skurnik / Haartman Institute / University of Helsinki==6$Z  Bd*8tsh @ ? XP3e4'80___PPT10.EE MSTEMPL 0   (  j  s *1 ?HY  oB  s *tsh*8 ? X(=^80___PPT10.E0   00(  B  s *tsh*8 ? X(=^80___PPT10.EP*   0L0 {(  C  HA$)?!  yERA-NET PathoGenoMics Meeting Bonn April 8, 2005 Mikael Skurnik, PhD Professor of Bacteriology University of Helsinki.z Z5CE3                      hh88H  0*8tsh ? XP3e4'___PPT10i.EP* +D=' $= @B +-  0L0 ,$(     0Z$    $ H  0*8tsh ? XP3e4'___PPT10i.EP* +D=' $= @B +D   0L0 C ; p 6(     0Ȯ      :  6 #"/s    . H#f)?  *Functional genomics of pathogenic bacteria++*  @`  H8 f)?:  PFunctional genomics, transcriptome analysis added with proteomics. Comparative genomics has an essential role. Research in this field in Finland is active on e.g. Helicobacter, Yersinia, E.coli and Campylobacter.0ofof3                 + B      @`   Hp f)?: -Pathogenic and non-pathogenic related species..-  @`fB   61 ?  fB   61 ?: ZB  s *1 ?: fB  61 ?::fB  61 ?: ZB / s *1 ?H  0*8tsh ? XP3e4'___PPT10i.EP* +D=' $= @B +   0L0  W(     0 C       W #" [ 3 HA!f)? ~v0___PPT106___PPT9 USQuality of Finnish cellular microbiology research is behind the international frontTT                @` 1 Hi#f)?  Cellular microbiology$0     @`  HTf)?r 8___PPT10F___PPT9(  1Mechanisms of the microbial invasion into body are a central point in pathogenesis research. Helps in understanding the differences between individuals on their susceptibility and resistance to infections Advances vaccine research Helps to develop more specific and efficient means to combat infections. D^^ &3$31  @`  H]f)?r  Mechanisms of invasiveness$  @`  HEf)?r HThe use of in vivo techniques both with conventional and transgenic animal models needs networking due to high costs. Does not replace exposure tests using human volunteers, however. BwBw @&33  @`   Hnf)?r "In vivo pathogenesis of infections(#"$"  @``B   01 ?rrfB   61 ?fB   61 ?ZB  s *1 ?fB  61 ?fB  61 ?ZB 2 s *1 ?  H  0*8tsh ? XP3e4'___PPT10i.EP* +D=' $= @B +   0L0   @ X 9 (   ~  s *Xo   o { |   X  #"    R   Hܘf)?:  >>Research on microbial ecology and populations related to health and disease of humans is a basis for all microbial pathogenicity studies. Two research fields of special importance can be highlighted (i) Research on microbial populations in the different parts of the gastrointestinal tract (ii) research on clonality within one species. More research is needed especially to characterize the gut microbiota and to develop DNA chip based high throughput diagnostics as well as to use comparative genomics (within species  between species). <WU3s   G [    P     @`   Hof)?:  !Microbial ecology and populations""! UFGHfB   61 ?  fB   61 ? ZB 6  s *1 ?:: fB   61 ?fB   61 ? H  0*8tsh ? XP3e4'___PPT10i.EP* +D=' $= @B +~   0L0 } u `P (     0 C    I    P #"z   % M H`!f)?"`   5New imaging techniques need to be developed further. 665  @`@ K HpE!f)?"`  LBioluminescence (and other) imaging techniques to follow infections in vivo MMK  @`n  H@f)?   The topic is under active research and is considered important both to basic and applied research (such as vaccine and antibiotic research).  @`J  Hf)?  FAntigenic diversity and variation. Bacterial cell surface structures. 6G#"$E  @`k  H}f)?  Research in these fields is at a high level in Finland and should be further supported and developed. Role of horizontal gene transfer.   @`!   Hf)?  ;Evolution of microbial virulence and antibiotic resistance <<:  @``B   01 ?fB   61 ?  fB   61 ? ZB  s *1 ?  fB  61 ?fB  61 ? ZB G s *1 ?  H  0*8tsh ? XP3e4'___PPT10i.EP* +D=' $= @B +   0L0   P ,> (  , ,  0\$&d  $ z t  , #"zW  $ , Hsf)?"` t  2This will be the basis of systems biology approach on infection biology. It gives essential data for studies on metabolic interactions and adaptations of host cells and bacteria. 0JkJk3  @`1 , H<f)?"` t  /Microarrays and proteomics of infected tissues 00"  #  @`% , HD$f)?"`  5New imaging techniques need to be developed further. 665  @`@ , H0 f)?"`  LBioluminescence (and other) imaging techniques to follow infections in vivo MMK  @`fB  , 61 ?t t fB  , 61 ?t ZB  , s *1 ?  t fB , 61 ?fB , 61 ?t ZB , s *1 ?H , 0*8tsh ? XP3e4'___PPT10i.EP* +D=' $= @B +z   0L0   @ (b (  ( (  0 !& d  !  @  ( #"@  ! ( Hi!f)?"` i@  wDatabases and especially the development of data analysis techniques have a key role in modern pathogenomics research. xx._      @` ( Hd~!f)?"`i  'Databases and data analysis techniques ((&  @` ( Hd!f)?"` @i Vaccination research has a long tradition, even though the research at National Public Health Institute has decreased considerably during the last years.   @`T  ( HPt!f)?"` i `Development of new bioassays for the identification of novel targets for therapy and vaccinationaa`  @`fB ( 61 ? @ fB ( 61 ? ZB ( s *1 ?  fB ( 61 ?@fB ( 61 ?@@ ZB ( s *1 ?i@iH ( 0*8tsh ? XP3e4'80___PPT10.EP*    0L0 O G 0 $ (  $ $  0d$   $   NB  $ #">Q  $ $ H0!f)?"` NB  #The topic of secondary pathologies induced in the host is included also in the EU FP6. A good record of patients exists in Finland, and gives a good opportunity for these studies.     @`m $ Hd!f)?"` B  OSecondary pathologies (eg. cancer and autoimmune diseases) induced in the host (PN$.  5  @` $ H$f)? N ;Many pathogens are unculturable. Some (new) unculturable microbes are considered important since they may be the causative agents of (infectious) chronic diseases. H      l  @` $ HQf)?  Unculturable microorganisms 0     @`fB  $ 61 ?B NB fB  $ 61 ?B ZB $ s *1 ?  B fB $ 61 ?NfB $ 61 ?NNB ZB $ s *1 ?NH $ 0*8tsh ? XP3e4'80___PPT10.EP* $  0L0 | t 2 (     0     H  Nl 2 #"Nl  E  H`} f)?"`1N Most bacterial species have prophages Bacteriophage genomes integrated into the bacterial genome in lysogenic state Are one of the causes of the genome plasticity of bacteria and central in the evolution of bacteria. B&Nf&N3fb      1   l  @`  Hxf)?"`1  wBacteriophages   @`  HTf)?1 Nl Phagetherapy as a complement to antibiotic therapy needs further investigation and may be an important aspect in the future treatment of diseases. Critical controlled information of bacteriophages and their in vivo behaviour needs to be gathered0cc3"                          @`  Hdf)? 1l  Phage therapy0    @`U  Hf)?1N  eBacteriophage-host bacterium interactions can be studied as an example in a systems biology approach.ff"  X  @``B   01 ? N fB   61 ?lNlfB   61 ?lZB  s *1 ?11lfB  61 ?NfB  61 ?NNlZB $ s *1 ?1NH  0*8tsh ? XP3e4'80___PPT10.EP* @   0L0    "( (     0<    d   h  " #"$ h    HȜf)?Dh  VThis information is essential in understanding the mechanisms of infections. Evasion of the host immune defence is under active research in Finland, also in MICMAN. NNYL X&3  3(L X  @`  Hؤf)? Dh  #Evasion of the host immune defence ($"$"  @`  Hf)?D This research calls for a holistic approach, the use of systems biology and e.g. microarray techniques. These topics are investigated in a number of MICMAN-funded projects, and need to be continued. Niag `&3  3BQ     `  @`8   HHf)? D BMetabolic interactions and adaptations of host cells and bacteria (CA$A  @``B   01 ? DDfB   61 ? h h fB   61 ?  h ZB  s *1 ?h fB  61 ? fB  61 ?h H  0*8tsh ? XP3e4'80___PPT10.EP*   0L0 OG (     0    | t\  #"  /S  \  H,f)?" t\ zCompanies on novel diagnostic approaches have been born in Finland, and research will give opportunities for further ones {{y  @`  H3f)?t"  +Novel diagnostic and screening approaches ,,+  @`fB   61 ?\fB   61 ?tZB  s *1 ?" t" fB  61 ?t\tfB  61 ?\t\H  0*8tsh ? XP3e4'80___PPT10.EP*   0L0  (     0@    | N   #" N    Hf)?N  zDespite the increasing use of various commercial probiotics, the mechanisms behind their claimed beneficial effects are either unknown or poorly characterized. It is important to gain new knowledge of probiotics for scientifically solid use of these preparations and for consumer protection. Research with new high throughput molecular methods should be supported in order to elucidate also mechanisms of host - normal microbiota interactions.   b1           @`+   Hf)?  'Probiotics, role of the resident flora ((&$"    @`fB   61 ? N fB   61 ? ZB  s *1 ? fB  61 ?NfB  61 ?NN H  0*8tsh ? 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