Unknown, rare and genetically determined diseases

Area-wise research

• Using multi-omics data to diagnose rare genetic diseases.
  
• Creating models of genetically determined human diseases using induced pluripotent cells.
  
• Creating a centre for biomodelling of disease processes in rodents and Danio rerio using genome editing technologies.
  
• Developing and testing of artificial intelligence-based detectors in wide population groups to detect children with rare, understudied congenital diseases for their early verification.
  
• Creating a registry of unknown, rare and genetically determined diseases.
  
• Creating a registry of congenital genetic cardiomyopathies in children.
  
• Developing personalized technologies for the treatment of familial hypercholesterolemia based on pheno- and genotype profiles of patients.
  
• Investigating the molecular mechanism of non-classical (non-monogenic) autoinflammatory diseases and searching for the directions for their targeted therapy.
  
• Searching for new directions of targeted therapy for congenital and acquired diseases with excessive calcification.
  
• Developing approaches to the creation and personalized use of gene therapy drugs for congenital genetic disorders of the neuromuscular and cardiovascular systems.

Expected results

A computational pipeline will be developed for basic collaborative analysis of whole-exome and RNA sequencing and metabolomic profiling. It is planned to allocate linear (LDLR and PCSK9 knock-out) mice and fish (Krox20, Sox10, Hb9, Sox10kaede) at the Centre.

Preclinical and clinical trials of anti-calcification drugs will be conducted.

The Cre / flox genetic tracing method will be developed and implemented for labeling embryonic stem cells in genetically modified experimental animal models and studying their hierarchy in early development.

Programmes will be developed for creating a bank of 2D and 3D cell cultures, and the most popular cell lines will be assessed as part of research conducted at the Centre.

A registry of congenital genetic cardiomyopathies in children will be created. Primary cell lines based on peripheral mononuclear cells and iPSC lines will be created.

Genetic testing of patients with a clinical diagnosis of familial hypercholesterolemia will be carried out. A particular focus will be on the study of the possibilities of personalized therapy for familial hypercholesterolemia based on pheno- and genotype profiles of patients.

Computational methods will be developed to integrate single-cell RNA sequencing data and exome sequencing results.

New transgenic knockout Danio Rerio model lines will be created to conduct experiments in neurobiology, obtain data on the role of neural crest cells and glial progenitor cells in the differentiation of other cell types in early development, and determine the role of embryonic glia in embryo development abnormalities.

The optimal serotype of adeno-associated virus will be chosen for further work with cells and tissues of the neuromuscular system, its tropism for myoblasts and other types of muscle cells will be studied in vitro, and the subsequent ability for full differentiation of myoblasts will be assessed.

Techniques for proteomic analysis will be developed and pilot experiments will be carried out. Computational methods will be developed to integrate the data of proteomic analysis and exome sequencing.

Methods for embryo cryopreservation and embryo transfer in laboratory rodents will be introduced, testing of three-dimensional cultivation of cells of LLC and other tumor lines (spheroids), preparation for three-dimensional cultivation of tumor organoid cultures (tumoroid) will be carried out.

New technologies will be developed to isolate and purify adeno-associated viruses (AAV), and additional analytical techniques for assessing the capsid protein ratio will be developed. Methods for transfection of plasmid DNA in suspension cultures of HEK293 cells in bioreactors will be improved.

It is planned to create an algorithm for a decision support system in lipidology to ensure a unified system approach to the management of familial hypercholesterolemia in primary care setting.

A search will be made for new causative genes of congenital and genetic human diseases.

Preclinical trials will be initiated for a drug for gene therapy of congenital neuromuscular diseases involving damage to the heart muscle and skeletal muscles.