Timofei Zatsepin

Associate Professor
Center of Life Sciences

Timofei is a strong scholar and entrepreneur with a solid background in oligonucleotide and siRNA chemistry. He received the Candidate of Science degree in Bioorganic Chemistry from M.V. Lomonosov Moscow State University (MSU) in 2003. After a year of research assistantship at the Laboratory of Chemistry of Nucleic Acids, MSU Department of Chemistry, Timofei was promoted to the Lab’s Research Associate. In year of 2004 Timofei became the Head of the oligonucleotide production unit at the Central Research Institute of Epidemiology (CRIE), Moscow, where he still maintains the position and is in charge of provision of synthetic oligonucleotides for a range of diagnostic and sequencing applications. Since 2012 Timofei is a Senior Research Associate at the MSU Laboratory of Chemistry of Nucleic Acids. He is also a cofounder of DNA-Synthesis – a company that provides oligonucleotide based services like synthesis of primers, probes and genes.

Timofei is a recipient of the Academia Europea Prize for the synthesis and evaluation of 2′-modified oligonucleotides, as well as awards and prizes from International Soros Science Educational Program, MSU and the Government of Russia among others. His publication record features such respected scientific journals in the field of organic chemistry as Nucleic Acids Research, RNA and PLoS One. Timofei is also an enthusiastic teacher with more than ten years of experience in preparing and reading lectures on biochemistry and molecular biology.

Timofei first joined Skoltech in 2013 as Associate Director of the Center for Functional Genomics, where he has established a high-class laboratory for oligonucleotide synthesis. In this capacity, he oversaw most of the Center’s scientific activities and plays the key role in Skoltech collaborations with a number of institutions, including MIT, Max Planck Institute in Dresden and MSU.

  • Targeted delivery of modified antisense/siRNA/sgRNA in vivo.
    We are working on the development of RNA-based therapeutics with improved efficacy, biodistribution and stability in vivo. We design and synthesis of heavily modified RNA for gene silencing and CRISPR-Cas9 gene editing to improve potency, efficacy and specificity. Then modified oligonucleotides are either packed in lipid nanoparticles or directly conjugated to the ligands of cellular receptors to enhance targeted delivery in vivo. We succeeded in synthesis and use of GalNAc-RNA conjugates for hepatocyte-specific delivery to the liver and now work with small molecules that bind to mannose, PSMA and folate receptors in macrophages, breast cancer cells and prostate cancer cells.
  • Functional studies of new targets for liver cancer/fibrosis therapy:
    –  Regulation of antitumor response via modulation of Ubr-ubiquitin ligases in vivo
    This project is focused on the development of a new approach that allows regulation of the activity of the N-end rule in clinically relevant settings by liver-specific delivery of Lipid NanoParticles loaded with highly potent siRNA probes against key components of the N-end rule pathway.
    - Role of DDX3 helicase in the translation process
    Application of the RNA interference method will provide us a stable DDX3 knockdown system to perform ribosomal profiling and deep RNA sequencing in vivo. The results of sequencing will allow us to reveal target mRNAs for DDX3 RNA helicase, hence, define and describe the exact role of DDX3 in translation in the mouse liver.
    - Role of LL35 lncRNA in the liver
    Using bioinformatic analysis we found a possible functional analog of the ncRNA DEANR1 in mouse – LL35 ncRNA and confirmed its expression in the mouse liver. Based on the published data we assume that ncRNA LL35 may be involved in the transcription regulation in the liver and can affect metabolic processes and various liver diseases in mice.
    - Mouse long non-coding RNA Gm14005 as a potential functional analog of human long non-coding RNA CYTOR
    Deeper insight into mechanism of CYTOR lncRNA action, as well as identification of its potency as an anti-cancer therapeutic target, require reliable animal models and further in vivo studies. To make a transfer from in vitro to in vivo research we identify the potential functional analog of CYTOR lncRNA in mice – lncRNA Gm14005. Investigation of Gm14005 functional roles and interactions both in vivo and in vitro will describe its potential application as a CYTOR analog in vivo.
  • Novel fluorescent oligonucleotide probes for DNA/RNA detection.
    We are working on the novel design of oligonucleotide probes for qPCR/ RT-qPCR. Currently we start a project devoted to evaluation of bladder cancer by droplet digital PCR (joint study with MSU and Institute of Urology).
Olga Sergeeva
Senior Research Scientist
Svetlana Dukova
Research Engineer
Nataliya Logvina
Research Scientist
Denis Melnik
PhD student
Arsen Mikaelyan
Research Scientist
Katerina Nagornova
Research Engineer
Tatiana Abakumova
Junior Research Scientist
Dominique Leboeuf
PhD student
Anna Fefilova
PhD student
Oxana Kovaleva
Research Intern
  • Instrumental Methods in Molecular Biology
This course is devoted to the principles of main instrumental methods that are used today in molecular biology. The aim of this course is to provide knowledge of modern methods for master students with little or no background in the field of molecular biology. A summary of modern approaches will introduce students to the general principles of methods in the biomedical research. By focusing on examples of the biomolecule purification and purity confirmation the idea of accurate studies will be explained. The course will provide a comprehensive summary of the major methods used nowadays in the field, except microsopy. Current trends will be reviewed, along with a discussion of methods application for common tasks. Some attention will be paid to minituarization of analytical devices for the use as POC (point-of-care).
  • RNA Biology
This course is devoted to the knowledge on the structures of RNA and RNA-protein complexes as well as their functioning in cells. The aim of this course is to provide an explanation of fundamental mechanisms such as translation, splicing and gene expression regulation based on the structural viewpoint. Thus the role of RNA in the maintenance of cell identity and cell metabolism will be defined. By focusing on modern techniques for RNA and RNA-protein structure and RNA modifications analysis, students will get aquainted with the approaches to study RNA input into cellular processes in vitro and in vivo.
The students will apply obtained knowledge and skills in presentations and a written exam. An examination commission, consisting of CTB faculty and of invited members, will conduct final evaluation of the overall product design completeness, quality of the results achieved, and of the presentations delivered.