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Advanced Nano and Microtechnologies Advanced Materials Structural Biology Gen. and Prot. of Plant Systems Molecular Medicine Brain and Mind Research Molecular Vet. Medicine

Dmitriy Chudakov Research Group

Research Group Leader
Researcher ID
Phone: +420 54949 8195
E-mail:
Office:

Research areas

  • T cell receptor (TCR) and immunoglobulin (IG) repertoires in health and disease
  • Autoimmunity
  • Hematopoietic stem cell transplantation

Main objectives

  • To develop new technologies for the efficient deep profiling of immune repertoires
  • To understand better the ensemble function of the adaptive immune system
  • To rationally improve therapies that modulate immune function 

Content of research

Every individual’s adaptive immune system is composed of tens of millions or more different T and B lymphocyte clones, each of which respectively expresses a distinct T cell receptor or antibody molecule. This tremendous diversity allows the immune system to generate receptors for a broad spectrum of antigens and to thereby ensure an efficient, targeted immune response. After the immune system has eliminated pathogens or diseased tissues, expanded pools of antigen-specific cells can subsequently persist for many years as memory cells, and these may therefore be used to track an individual‘s history of infections, vaccinations, and possibly even autoimmune and anti-tumor responses. Next generation sequencing (NGS) techniques are capable of reading millions of short DNA fragments, and thus allow deep analysis of the diversity of antibodies and T cell receptors within an individual repertoire. My team employs NGS to study adaptive immunity and, in parallel, also works on advanced molecular technologies and specialized software solutions that collectively allow us to minimize quantitative biases, eliminate input bottlenecks and efficiently correct PCR and sequencing errors to ensure accurate and quantitative analysis of T cell receptor and antibody repertoires.

list / cards

Name and position

E-mail

Phone

Dmitriy Chudakov, Ph.D.
Research Group Leader
+420 54949 8195
Alexey Nikolayevich Nikolayevich Davydov
Specialist
+420 54949 5892
Daniela Komrsková, Ph.D.
Technician
+420 54949 7922, +420 532 234 623
Jana Mokrá
+420 54949 6997
Anton Pereverzev
Ivan Zviagin

SELECTED PUBLICATIONS

2017

  • DAVEY, M S; WILLCOX, C R; JOYCE, S P; LADELL, K; KASATSKAYA, S A; MCLAREN, J E; HUNTER, S; SALIM, M; MOHAMMED, F; PRICE, D A; CHUDAKOV, D M; WILLCOX, B E, 2017:Clonal selection in the human V delta 1 T cell repertoire indicates gamma delta TCR-dependent adaptive immune surveillance.. Nature communications
  • DAVEY, MS; WILLCOX, CR; JOYCE, SP; LADELL, K; KASATSKAYA, SA; MCLAREN, JE; HUNTER, S; SALIM, M; MOHAMMED, F; PRICE, DA; CHUDAKOV, DM; WILLCOX, BE, 2017:Clonal selection in the human V delta 1 T cell repertoire indicates gamma delta TCR-dependent adaptive immune surveillance. NATURE COMMUNICATIONS 8
  • LEVINE, AG; MEDOZA, A; HEMMERS, S; MOLTEDO, B; NIEC, RE; SCHIZAS, M; HOYOS, BE; PUTINTSEVA, EV; CHAUDHRY, A; DIKIY, S; FUJISAWA, S; CHUDAKOV, DM; TREUTING, PM; RUDENSKY, AY, 2017:Stability and function of regulatory T cells expressing the transcription factor T-bet. NATURE 546 (7658), p. 421 - +.
  • SHAGIN, DA; TURCHANINOVA, MA; SHAGINA, IA; SHUGAY, M; ZARETSKY, AR; ZUEVA, OI; BOLOTIN, DA; LUKYANOV, S; CHUDAKOV, DM, 2017:Application of nonsense-mediated primer exclusion (NOPE) for preparation of unique molecular barcoded libraries. BMC GENOMICS 18
  • SHUGAY, M; ZARETSKY, AR; SHAGIN, DA; SHAGINA, IA; VOLCHENKOV, IA; SHELENKOV, AA; LEBEDIN, MY; BAGAEV, DV; LUKYANOV, S; CHUDAKOV, DM, 2017:MAGERI: Computational pipeline for molecular-barcoded targeted resequencing. PLOS COMPUTATIONAL BIOLOGY 13 (5)
  • ZVYAGIN, IV; MAMEDOV, IZ; TATARINOVA, OV; KOMECH, EA; KURNIKOVA, EE; BOYAKOVA, EV; BRILLIANTOVA, V; SHELIKHOVA, LN; BALASHOV, DN; SHUGAY, M; SYCHEVA, AL; KASATSKAYA, SA; LEBEDEV, YB; MASCHAN, AA; MASCHAN, MA; CHUDAKOV, DM, 2017:Tracking T-cell immune reconstitution after TCR alpha beta/CD19-depleted hematopoietic cells transplantation in children. LEUKEMIA 31 (5), p. 1145 - 1153.

2016

  • BAGAEV, DV; ZVYAGIN, IV; PUTINTSEVA, EV; IZRAELSON, M; BRITANOVA, OV; CHUDAKOV, DM; SHUGAY, M, 2016:VDJviz: a versatile browser for immunogenomics data. BMC GENOMICS 17
  • BRITANOVA, OV; SHUGAY, M; MERZLYAK, EM; STAROVEROV, DB; PUTINTSEVA, EV; TURCHANINOVA, MA; MAMEDOV, IZ; POGORELYY, MV; BOLOTIN, DA; IZRAELSON, M; DAVYDOV, AN; EGOROV, ES; KASATSKAYA, SA; REBRIKOV, DV; LUKYANOV, S; CHUDAKOV, DM, 2016:Dynamics of Individual T Cell Repertoires: From Cord Blood to Centenarians. JOURNAL OF IMMUNOLOGY 196 (12), p. 5005 - 5013.
  • PLITAS, G; KONOPACKI, C; WU, KM; BOS, PD; MORROW, M; PUTINTSEVA, EV; CHUDAKOV, DM; RUDENSKY, AY, 2016:Regulatory T Cells Exhibit Distinct Features in Human Breast Cancer. IMMUNITY 45 (5), p. 1122 - 1134.
  • SARKISYAN, KS; BOLOTIN, DA; MEER, MV; USMANOVA, DR; MISHIN, AS; SHARONOV, GV; IVANKOV, DN; BOZHANOVA, NG; BARANOV, MS; SOYLEMEZ, O; BOGATYREVA, NS; VLASOV, PK; EGOROV, ES; LOGACHEVA, MD; KONDRASHOV, AS; CHUDAKOV, DM; PUTINTSEVA, EV; MAMEDOV, IZ; TAWFIK, DS; LUKYANOV, KA; KONDRASHOV, FA, 2016:Local fitness landscape of the green fluorescent protein. NATURE 533 (7603), p. 397 - 401.
  • TURCHANINOVA, MA; DAVYDOV, A; BRITANOVA, OV; SHUGAY, M; BIKOS, V; EGOROV, ES; KIRGIZOVA, VI; MERZLYAK, EM; STAROVEROV, DB; BOLOTIN, DA; MAMEDOV, IZ; IZRAELSON, M; LOGACHEVA, MD; KLADOVA, O; PLEVOVA, K; POSPISILOVA, S; CHUDAKOV, DM, 2016:High-quality full-length immunoglobulin profiling with unique molecular barcoding. NATURE PROTOCOLS 11 (9), p. 1599 - 1616.

2015

  • BOLOTIN, DA; POSLAVSKY, S; MITROPHANOV, I; SHUGAY, M; MAMEDOV, IZ; PUTINTSEVA, EV; CHUDAKOV, DM, 2015:MiXCR: software for comprehensive adaptive immunity profiling. NATURE METHODS 12 (5), p. 380 - 381.
  • FENG, YQ; VAN DER VEEKEN, J; SHUGAY, M; PUTINTSEVA, EV; OSMANBEYOGLU, HU; DIKIY, S; HOYOS, BE; MOLTEDO, B; HEMMERS, S; TREUTING, P; LESLIE, CS; CHUDAKOV, DM; RUDENSKY, AY, 2015:A mechanism for expansion of regulatory T-cell repertoire and its role in self-tolerance. NATURE 528 (7580), p. 132 - 136.
  • LUKER, KE; PATA, P; SHEMIAKINA, II; PEREVERZEVA, A; STACER, AC; SHCHERBO, DS; PLETNEV, VZ; SKOLNAJA, M; LUKYANOV, KA; LUKER, GD; PATA, I; CHUDAKOV, DM, 2015:Comparative study reveals better far-red fluorescent protein for whole body imaging. SCIENTIFIC REPORTS 5
  • SHUGAY, M; BAGAEV, DV; TURCHANINOVA, MA; BOLOTIN, DA; BRITANOVA, OV; PUTINTSEVA, EV; POGORELYY, MV; NAZAROV, VI; ZVYAGIN, IV; KIRGIZOVA, VI; KIRGIZOV, KI; SKOROBOGATOVA, EV; CHUDAKOV, DM, 2015:VDJtools: Unifying Post-analysis of T Cell Receptor Repertoires. PLOS COMPUTATIONAL BIOLOGY 11 (11)
  • SHUGAY, M; LUKYANOV, S; CHUDAKOV, DM, 2015:Sequencing rare T-cell populations. ONCOTARGET 6 (37), p. 39393 - 39394.

2014

  • SHUGAY, M; BRITANOVA, OV; MERZLYAK, EM; TURCHANINOVA, MA; MAMEDOV, IZ; TUGANBAEV, TR; BOLOTIN, DA; STAROVEROV, DB; PUTINTSEVA, EV; PLEVOVA, K; LINNEMANN, C; SHAGIN, D; POSPISILOVA, S; LUKYANOV, S; SCHUMACHER, TN; CHUDAKOV, DM, 2014:Towards error-free profiling of immune repertoires. NATURE METHODS 11 (6), p. 653 - +.

2013

  • BOLOTIN, DA; SHUGAY, M; MAMEDOV, IZ; PUTINTSEVA, EV; TURCHANINOVA, MA; ZVYAGIN, IV; BRITANOVA, OV; CHUDAKOV, DM, 2013:MiTCR: software for T-cell receptor sequencing data analysis. NATURE METHODS 10 (9), p. 813 - 814.
  • LINNEMANN, C; HEEMSKERK, B; KVISTBORG, P; KLUIN, RJC; BOLOTIN, DA; CHEN, XJ; BRESSER, K; NIEUWLAND, M; SCHOTTE, R; MICHELS, S; GOMEZ-EERLAND, R; JAHN, L; HOMBRINK, P; LEGRAND, N; SHU, CJ; MAMEDOV, IZ; VELDS, A; BLANK, CU; HAANEN, JBAG; TURCHANINOVA, MA; K, 2013:High-throughput identification of antigen-specific TCRs by TCR gene capture. NATURE MEDICINE 19 (11), p. 1534 - +.

2012

  • LUKER, KE; MIHALKO, LA; SCHMIDT, BT; LEWIN, SA; RAY, P; SHCHERBO, D; CHUDAKOV, DM; LUKER, GD, 2012:In vivo imaging of ligand receptor binding with Gaussia luciferase cornplementation. NATURE MEDICINE 18 (1), p. 172 - 177.
  • SHEMIAKINA, II; ERMAKOVA, GV; CRANFILL, PJ; BAIRD, MA; EVANS, RA; SOUSLOVA, EA; STAROVEROV, DB; GOROKHOVATSKY, AY; PUTINTSEVA, EV; GORODNICHEVA, TV; CHEPURNYKH, TV; STRUKOVA, L; LUKYANOV, S; ZARAISKY, AG; DAVIDSON, MW; CHUDAKOV, DM; SHCHERBO, D, 2012:A monomeric red fluorescent protein with low cytotoxicity. NATURE COMMUNICATIONS 3

GRANTY

  • Advanced bioinformatics platform for PERsonalised cancer IMmunotherapy (633592), H2020 - Societal challenges - Health, 2015 - 2018

1. Ratiometric genetically encoded fluorescent sensors for measurement of intracellular pH values

Supervisor: Dmitriy Chudakov, Ph.D., DSc.

Annotation:

Intracellular pH influences a lot of processes in cellular cytoplasm and intracellular compartments. [1-10]. Fluorescent proteins have many advantages compared to chemical fluorescent dyes in living cell imaging, including less invasive measurement and possibility of tethering the reporter to any cellular organelle or compartment. Sensitivity to pH has been used to develop genetically engineer encodable pH indicators [11]. Genetically encoded fluorescent pH reporters enable to measure spatial and temporal changes of pH in dynamics. To date, in spite of development of different geneticaly encoded fluorescent-based pH indicators, both single-color and ratiometric pH sensors have been ultimately used rather to detect the direction of pH changes, than to measure exact pH value in live cell microscopy. The project will be dedicated to creation of ratiometric pH sensors based on pH-sensitive GFP mutants and highly pH-independent red fluorescent protein which can be used for precise imaging of pH value for a great variety of biological events and signals.

1. Putney LK, Barber DL. J Biol Chem. 2003;278:44645
2. Hunte C, Screpanti E, Venturi M, Rimon A, Padan E, Michel H. Nature. 2005;435:1197
3. Gruenberg J, Stenmark H. Nat Rev Mol Cell Biol. 2004;5:317
4. Wakabayashi I, Poteser M, Groschner K. J Vasc Res. 2006;43:238
5. Izumi H, Torigoe T, Ishiguchi H, Uramoto H, Yoshida Y, Tanabe M, Ise T, Murakami T, Yoshida T, Nomoto M, Kohno K. Cancer Treat Rev. 2003;29:541
6. Carnell L, Moore HP. J Cell Biol. 1994;127:693
7. Chesler M. Physiol Rev. 2003;83:1183
8. Tantama M. J. Am. Chem. Soc., 2011, 133 (26), pp 10034–10037
9. Casey, J.R.; Grinstein, S.; Orlowski, J. Nat. Rev. Mol. Cell Biol. 2010, 11, 50–61
10. Orij, R.; Brul, S.; Smits, G.J. Biochim. Biophys. Acta. 2011, 1810, 933–944
11. Sylvie Lalonde, David W Ehrhardt, Wolf B Frommer. Current Opinion in Plant Biology. Volume 8, Issue 6, December 2005, Pages 574–581

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