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Young Researchers and Professionals
| Project leader |
Knežević Ana |
| Project co-leader: |
Dr. Damir Marjanović |
| Administering organization: |
Genos Ltd, Planinska 1, 10000 Zagreb, Croatia, www.genos.hr
Authorized person: Dr. Damir Marjanović, Director of Research and Development
Phone: 01 2352 660 begin_of_the_skype_highlighting 01 2352 660 end_of_the_skype_highlighting; fax: 2352 663; email: info@genos.hr
OIB: 17560201884 |
| Partner Institution/Company: |
Genos L.t.d. |
| Grant type: |
3C |
| Project title: |
High throughput contract analysis of plasma glycans |
| Project summary: |
Genos Ltd is a vibrant bioscience company (SME) primarily oriented towards contract
research and development in the field of DNA analysis and glycobiology. It performs
contract analysis and method development for numerous companies, hospitals and
universities in Croatia and abroad. High throughput quantitative glycan analysis is one of the
areas where Genos wants to expand its activity because currently active laboratories in
Europe cannot fulfill growing demand. High-throughput quantitative HPLC analysis of
glycans was developed three years ago in Dublin, and a huge advantage of Genos Ltd is the
already existing collaboration with Dr. Olga Gornik and Ana Knežević who were guest
researchers in Dublin-Oxford Glycobiology laboratory when the method has been
developed. Through this project, Ana Knežević will be appointed as a Head of the newly
established Glycobiology Division in Genos. Due to her previous contacts and experience,
she will also continue her research collaboration with academic institutions in both Croatia
and abroad.
Glycosylation is a post-translational modification that enriches protein complexity and
function. Multiple proteins are modified by covalently bound glycans, which is important for
normal physiological processes, including protein folding, degradation and secretion, cell
signaling, immune function and transcription. This process is not template driven, so that
the complexity of the glycoproteome is estimated to be several orders of magnitude greater
than for the proteome itself. Dysregulation of glycosylation is implicated in a wide range of
diseases, including cancer, diabetes, cardiovascular, congenital, immunological and
infectious disorders. Protein based medicaments (immunoglobulins, erythropoietin, etc) are
in use for autoimmune diseases, tumors and anemia but sometimes these medicaments are
not efficient because of inadequate glycosylation. Protein based medicaments are often
synthesized in bacterial cells or cell cultures and these conditions do not always correspond
to glycosylation environment in normal physiological cell. Result can be a protein with
correct amino acid sequence but with different pattern of glycosylation. As glycosylation
controls protein targeting and in general its proper function, the efficiency of that
medicament is frequently reduced. To develop efficient protein based medicaments but also
functional recombinant protein for other purposes, it is necessary to analyze glycosylation of
native proteins, as any progress can be possible only if we know and understand the natural
processes. |
| Hrvatski sažetak: |
Genos d.o.o. je mala tvrtka koja se bavi bioznanošću, a u prvom redu je orijentirana na istraživanje i razvoj u području analize DNA i glikobiologije. Obavlja ugovorne analize te razvija metode za brojne tvrtke, bolnice i sveučilišta u Hrvatskoj i u inozemstvu. Trenutno djelatni laboratoriji u Europi ne mogu ispuniti zahtjeve potražnje u području kvantitativne analize glikana metodom visoke propusnosti te stoga tvrtka Genos želi proširiti svoju djelatnost u dotičnom području. Visoko propusna kvantitativna HPLC analiza glikana razvijena je prije tri godine u Dublinu, a velika prednost Genosa je već postojeća suradnja sa Dr. Olgom Gornik i Anom Knežević koje su sudjelovale u razvijanju metode u Dublin-Oxford Glycobiology laboratoriju. Kroz ovaj projekt, Ana Knežević će biti imenovana voditeljicom Odjela za glikobiologiju u sklopu tvrtke Genos. Zbog svojih prethodnih kontakata i iskustava, Ana Knežević će nastaviti produktivnu znanstvenu suradnju s akademskim institucijama u Hrvatskoj i u inozemstvu.
Glikozilacija je posttranslacijska modifikacija proteina koja obogaćuje njihovu složenost i funkciju. Mnogi proteini su izmijenjeni kovalentno vezanim glikanima, što je važno za normalne fiziološke procese, uključujući smatanje proteina, razgradnju i izlučivanje, stanično signaliziranje, imunološke funkcije i prepisivanje slijeda DNA. Proces glikozilacije se ne odvija po kalupu, zbog čega se procjenjuje da je složenost glikoproteoma za nekoliko redova veličine veća nego za sam proteom. Poremećaji glikozilacije se javljaju u širokom rasponu bolesti, uključujući rak, dijabetes, kardiovaskularne, urođene, imunološke i zarazne bolesti. Lijekovi temeljeni na proteinima se koriste u liječenju autoimunih bolesti, tumora i anemija, no neodgovarajuća glikozilacija takvih lijekova može biti razlog njihove neučinkovitosti. Ovakvi lijekovi se često sintetiziraju u bakterijskim stanicama ili staničnim kulturama, ali ti uvjeti ne odgovaraju uvijek normalnim fiziološkim uvjetima glikozilacije. To može rezultirati proteinom sa ispravnim aminokiselinskim slijedom, ali s različitim uzorkom glikozilacije. Efikasnost lijeka u tom slučaju može biti smanjena s obzirom da glikozilacija sudjeluje u usmjeravanju proteina na ciljno mjesto djelovanja, ali i općenito na funkciju tog proteina. Analiza glikozilacije nativnih proteina predstavlja neophodan korak u razumijevanju prirodnih procesa te razvijanju učinkovitih lijekova na bazi proteina kao i rekombinantnih proteina upotrebljivih za druge svrhe.
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| Amount requested from UKF: |
84.000,00 HRK |
| Amount of matching funding: |
361.700,00 HRK |
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