Biennial Report 2011–2012

protein contains a bHLH domain and a PAS domain, which
are the common structures present in the HIF family. IPAS expression
in hepatoma cells selectively impairs the induction of
hypoxia-inducible genes regulated by HIF-1 and results in retarded
tumour growth and tumour vascular density in vivo. In
mice, IPAS was selectively expressed in Purkinje cells of the cerebellum
and in the corneal epithelium of the eye. Moreover,
the expression of IPAS in the cornea correlates with low VEGF
gene expression under hypoxic conditions.
We established that an essential splicing factor is involved in
oxygen-dependant pre-mRNA splicing regulation. Reducing
cellular expression of this factor changes splicing profile to hypoxic
characteristic. Overexpression of this factor moves splicing
pattern to normoxic characteristic.
Thus we identified hypoxia dependable pre-mRNA splicing
regulator which might reprogram cellular events and could not
only be useful for the potential therapeutic applications but
also for their application as an analytic tool.
This work was supported by the Framework 7 program (project
Metoxia).
Molecular epidemiology of
Mycobacterium tuberculosis
Tuberculosis (TB) caused by M. tuberculosis complex bacteria
remains a serious health problem in Lithuania. The rates
of incidence, particularly multidrug-resistant tuberculosis
(MDR TB) are one of the highest in the European Society.
The median survival for MDR TB patients during 2002-
2008 year in Lithuania was 4.1 year (Balabanova et al, BMJ
Open, 2011). The aim of this ongoing project is to characterize
in detail population of M. tuberculosis that circulates
in Lithuania including the genetic determinants of drug resistance.
The research was carried out in close collaboration
with Infectious Diseases and Tuberculosis Hospital, affiliate
of public institution Vilnius University Hospital Santariskiu
Klinikos. Genotyping of M. tuberculosis clinical strains was
performed by reference techniques (24-locus MIRU-VNTR
typing, spoligotyping) and polymorphisms of M. tuberculosis
genome were identified by direct sequencing.
In 2011-2012, we continued genotyping of M. tuberculosis
strains recovered from TB patients living in Vilnius. Overall,
From left to right MoBiLi project scientist Dr. S.Laurinavičius,
master student A.Ščerbakovaitė, group leader Dr. A.Kanopka and
bioengineer L.Vilys
the results of this study confirmed that stabilization of TB situation
is occurring. However, many of most dangerous transmission
chains have not been yet broken. Moreover, the new
clusters consisting of MDR and extensively drug resistant
(XDR) strains are emerging. In the frame of drugs resistance,
we focussed in search for the mutations associated with resistance
to aminoglycosides, capreomycin, and pyrazinamide
including the search for the novel targets involved in resistance
outside of well-known hot spot regions of the M. tuberculosis
chromosome. The results demonstrated that the mutations
causing kanamycin resistance, particularly in the 3’ region
of the rrs gene and in the promoter of the eis gene could
be an important driving force for the emergence and spread
of XDR TB strains in Lithuania. Identification of the mutations
in the pncA gene could be useful tool for the detection
of resistance to pyrazinamide and could serve as auxiliary subtyping
technique for a better differentiation of drug-resistant
strains as well.
This work was supported by European Community’s Seventh
Framework Programme (FP7/2007-2013) under grant agreement
FP7-223681 and the Agency for Science, Innovation
and Technology (MITA) under grant agreements 31V-87 and
31V-99.
Reference: de Beer et al., J. Clin. Microbiol. 2012, 50(3):662-9.
Vilnius University Institute of Biotechnology Biennial report for 2011–2012 53