R. M. Abdeev

Integrated network analysis of transcriptomic and proteomic data in psoriasis

BackgroundPsoriasis is complex inflammatory skin pathology of autoimmune origin. Several cell types are perturbed in this pathology, and underlying signaling events are complex and still poorly understood.ResultsIn order to gain insight into molecular machinery underlying the disease, we conducted a comprehensive meta-analysis of proteomics and transcriptomics of psoriatic lesions from independent studies. Network-based analysis revealed similarities in regulation at both proteomics and transcriptomics level. We identified a group of transcription factors responsible for overexpression of psoriasis genes and a number of previously unknown signaling pathways that may play a role in this process. We also evaluated functional synergy between transcriptomics and proteomics results.ConclusionsWe developed network-based methodology for integrative analysis of high throughput data sets of different types. Investigation of proteomics and transcriptomics data sets on psoriasis revealed versatility in regulatory machinery underlying pathology and showed complementarities between two levels of cellular organization.

Preparation and properties of Clostridium thermocellum lichenase deletion variants and their use for construction of bifunctional hybrid proteins.

Major properties (pH and temperature optimum, stability) of lichenase (b-1,3-1,4-glucanase) deletion variants from Clostridium thermocellum were comparatively studied. The deletion variant LicBM2 was used to create hybrid bifunctional proteins by fusion with sequences of the green fluorescent protein (GFP) from Aequorea victoria. The data show that in hybrid proteins both GFP and lichenase retain their major properties, namely, GFP remains a fluorescent protein and the lichenase retains activity and high thermostability. Based on the results of this investigation and results that have been obtained earlier, the use of the deletion variants of lichenase and the bifunctional hybrid proteins as reporter proteins is suggested.

Expression of a Thermostable Bacterial Cellulase in Transgenic Tobacco Plants

The bacterial gene of the thermostable endo-β-1,4-glucanase (cellulase) was shown to retain its activity and substrate specificity when expressed in transgenic tobacco plants. The leader peptide of the carrot extensin was efficient in transferring the bacterial enzyme into the apoplast. The expression of the bacterial cellulase gene leads to changes in the plant tissue morphology. In the transgenic plant lines, regeneration of primary shoots from callus occurred at the three to five times higher cytokinin (6-BAP) concentration than in control plants. The transgenic plants that expressed the bacterial gene exhibited increased bushiness and altered leaf shape. The transgenic plants developed can be used as models for studying the cellulases role and function in plants.

Transgenic Plants as a Tool for Plant Functional Genomics

Functional genomics aim to discover the biological function of particular genes and to uncover how sets of genes and their products work together. Transgenic plants are proving to be powerful tools to study various aspects of plant sciences. The emerging scientific revolution sparked by genomics based technologies is producing enormous amounts of DNA sequence information that, together with plant transformation methodology, is opening up new experimental opportunities for functional genomics analysis.

[Population analysis and determination of the ethnic background are necessary in the study of multifactorial diseases: a study using the Dagestan population as a model].

Psoriasis, a multifactorial disease with genetic predisposition, has been used as an example to study the role of the ethnic background in multifactorial diseases in the Dagestan population. The individual information card (IIC) is proposed as the main tool for correct collection and processing of information. The results of the study demonstrate that the Dagestan population is a convenient and adequate model population for studying multifactorial diseases, such as psoriasis, and may serve as an object for studying the role of heredity in the etiologies and pathogeneses of this and other multifactorial diseases.

A comparative analysis of the molecular genetic processes in the pathogenesis of psoriasis and Crohn’s disease

A comparative bioinformatics analysis of the molecular genetic processes in the pathogenesis of multifactorial diseases—psoriasis and Crohn’s disease—was performed using the results of microarray experiments deposited with the GEO DataSets database. A number of genes and molecular genetic processes common to both pathologies were found. The involvement of several transcription factors, including AP-1 transcription factors, in the pathogeneses of both psoriasis and Crohn’s disease was postulated.

Transcription factor AP-1 components as psoriasis candidate genes

Psoriasis is a multifactorial autoimmune skin disease widely spread in the Caucasoid population. Similar to other complex genetically determined pathologies, the success in treating psoriasis can be reached with the discovery of the molecular genetic mechanisms triggering the pathogenesis, including the search for the candidate target genes for drugs. This work, utilizing bioinformatics analysis of transcriptomics data, demonstrated that the genes for transcription factor AP-1 components can be regarded as psoriasis candidate genes.

Comparative analysis of N-acetylation polymorphism in humans as determined by phenotyping and genotyping

The N-acetylation polymorphisms of volunteers from the Moscow population analyzed by phenotyping and genotyping have been compared. The ratios between the proportions of fast acetylators (FAs) and slow acetylators (SAs) estimated by phenotyping and genotyping do not differ significantly from each other (47 and 44%, respectively). The absolute acetylation rate widely varies in both FAs and SAs. The NAT2 genotype and allele frequencies in the population sample have been calculated. The most frequent alleles are NAT2*4 (a “fast” allele), NAT2*5, and NAT2*6 (“slow” alleles); the most frequent genotypes are NAT2*5/*5, NAT2*4/*6, and NAT2*4/*5. Comparative analysis of N-acetylation polymorphism estimated by phenotyping and genotyping in the same subjects has shown a complete concordance between the phenotype and genotype in only 62 out of 75 subjects (87%). Comparative characteristics and presumed applications of the two approaches (quantitative estimation of acetylation rate and qualitative determination of the acetylator genotype) to the identification of individual acetylation status are presented.

Morphology and Phytohormone Content in Transgenic Tobacco Plants Expressing Bacterial Thermostable Cellulase

Expression of the bacterial gene for thermostable β-1,4-glucanase (cellulase) from Clostridium thermocellum in transgenic tobacco plants was shown to produce significant changes in tobacco plant structure and activities. The transgenic plants differed in their growth rate and morphology, and their hormonal status was affected. Thus, the transgenic plants expressing the gene for thermostable bacterial cellulase are a convenient model to study the role of β-1,4-glucanases in plant physiological processes.

Exploring the Properties of Thermostable Clostridium thermocellum Cellulase CelE for the Purpose of Its Expression in Plants

The main properties (pH and temperature range, stability, substrate specificity) of the modified cellulase CelE (endo-β-1,4-glucanase) from Clostridium thermocellum have been analyzed with the goal of its expression in plants. The modified enzyme is similar to plant cellulases. Deletions in the N-terminus of the enzyme do not affect its biochemical properties. Based on the present investigation, we conclude that the modified β-1,4-glucanase CelEM1, when expressed in plants, will be a good model to study the role of cellulases in plants.