Research 

Proteome encoded by Chromosome 18: 
Russian Part of the International Human Proteome Project

The Institute is a member of the International Chromosome-centric Human Proteome Project.

Transcriptome and proteomic profiling of the expression products of genes of human chromosome 18 in three types of biomaterial was carried out (Zgoda et al., 2013; Ponomarenko et al., 2014)

A method for detecting ultra-low-copy proteins has been developed, which allows measurements with a sensitivity of up to 10-18 M (according to BSA) (Kopylov et al., 2013).

Comparative analysis of human chromosomes based on post-genomic data showed minimal differences between chromosomes. For the Russian part of the project, chromosome 18 was selected for the optimal ratio of the number of protein-coding genes and their medical significance (Ponomarenko et al., 2012) 

Proteomics has reached a stage when more attention and curiosity need to be exerted in the identification of every novel protein in order to expand the unusual types of biomaterials and/or conditions. 

Postgenomic analytics for precision medicine
and digital QR code of health

Mass spectrometric analysis of plasma/serum metabolites for the development of diagnostic methods and assessment of the risk of socially significant diseases - prostate cancer, lung cancer, colorectal cancer, diabetes, neurodegenerative diseases, cardiovascular diseases

The optimization of drug therapy according to the personal characteristics of patients

The standard of a human digital image, which includes the metabolomic data sufficient to make an accurate assessment of general health and carry out precision diagnostics of a wide range of diseases

It was shown that the metabolomics data can be converted by SantaOmics into a standardized scale that can substitute actual concentration measurements, thus making the metabolomics data directly comparable with each other as well as with reference data presented on the same scale

Nanotechnology for one damaged molecule catching

Using of  the atomic force microscopy (AFM) as a molecular detector for detection of proteins in solutions at low concentrations, and also for determination of functional properties of single biomolecules, including the activity of individual molecules of enzymes

(AFM)-based detection of hepatitis C virus (HCV) particles in serum samples using a chip with an aptamer-functionalized surface (APTA-based AFM chip)

The detection of target nucleic acid molecules can be carried out with high sensitivity using sensor chips. Examples of the applications of such chips for the detection of cancer-associated microRNAs in plasma samples of patients with diagnosed prostate cancer are given. The results obtained herein are useful for the development of highly sensitive nanowire-based diagnostic systems for the revelation of (prostate) cancer-associated microRNAs in human plasma.

Bioinformatics, data-analysis and computer technologies
for detecting biomarkers, pharmacological targets and basic structures of new drugs

The algorithm of PASS program was used for the first, second, and third classes Drug-Drug Interactions prediction.

A novel method has been implemented for analyzing quantitative structure-activity relationships (QSAR) and predicting the activity of new substances; its advantages have been demonstrated in comparison with the number of other widely used QSAR methods.

A meta-analysis of the neXtProt knowledge base is proposed for theoretical prediction of the number of different proteoforms that arise from alternative splicing (AS), single amino acid polymorphisms (SAPs), and posttranslational modifications (PTMs).

Proteomic Cinderella: Customized analysis of bulky MS/MS data in one night

Concept-centered semantic maps were created based on a text-mining analysis of PubMed for examines the structure of the social networking environment generated by PubMed users

 

Gene-editing for human health and research

 A proteome-wide analysis combined with the editing of target genes and/or chromosomes will probably end up as a springboard into the next phase of the C-HPP.

Development of genetic engineering solutions in the field of creation of CRISPR/Cas genome editing systems.

Modulation of suppressor activity of regulatory T cells by induction of alternative splicing of FoxP3 pre-mRNA.

Obtaining model cultures of cells of the human immune system with improved by genetic editing, therapeutic properties.

Improvement of RNA and DNA detection systems based on Cas13 and Cas12 CRISPR effectors.

Targeted intervention in the genome of living organisms has allowed to solve issues related the creation of modified species of bacteria, plants and animals with new valuable properties and cellular models.

Works are aimed to the search and genetic engineering design of new CRISPR/Cas systems, i.e. the design and study of new editing systems and the development of the necessary methodological regulations.

The development of methods for a simplified one-step purification of recombinant Cas13 and Cas12 effectors after heterologous expression and for the standardization of their collateral ribonuclease activity. In a collaboration with the Tyumen State University, the assays for the in-field diagnostics of phytopathogens will be developed based on a combination of isothermal amplification of nucleic acids with CRISPR/Cas detection of target amplicons.

The CRISPR-Cas9 genetic editing system was used to study cancer stem cells. It was used to obtain colorectal adenocarcinoma cells CaCo-2 and HT-29 with a knockout stem cell marker CD133. The obtained clones were used to study the role of CD133 in the manifestation of the properties of cancer stem cells in vitro (Gisina et al. 2021).

The role of proteins of the p53 family in the regulation of keratinization processes in normal and pathological conditions is investigated. Modification of the activity of these proteins in cells using gene knockdown and knockout technologies. The obtained genetically modified keratinocyte lines with a knockout of the p53 and p63 genes showed features of differentiation and functioning.

A double sgRNA approach and method of marker-free selection, using inhibition of ATP1A1 by Ouabain was approach to enhance the efficiency of gene knockouts, specific gene editing and targeted deletion of specific protein domains. These methods will advance the methodology for the next phase of C-HPP.

Currently, the use of splice switching oligonucleotides (SSO) is considered one of the most specific methods of modulating the realization of genetic information and is considered one of the methods of genetic editing at the mRNA level. It has been shown that EndoG endonuclease is capable of inducing SSO and modulating alternative mRNA splicing of the catalytic subunit of telomerase hTERT (D.D. Zhdanov et al. 2019; Zhdanov et al. 2019) and DNase 1 (Zhdanov et al. 2020). Using PSO to the mRNA of the Rad51A protein, it was possible to increase cell survival under genotoxic stress (Gladilina et al. 2022).

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