Laboratory of molecular technologies
In our research we apply synthetic biology principles to study redox signaling, to develop molecular tools for in vivo imaging, metabolic engineering and optogenetics. In addition, we study molecular mechanisms of ischemic pathology, signaling in cancer cells, an interplay between calcium and reactive oxygen species and other relevant topics. The central principle of our research is trans-species and even trans-kingdom transfer of molecular blocks in order to obtain engineered living system with new properties. Our achievements in the field of redox biology and fluorescent microscopy include development of sensors for important redox active compounds within living cells, novel tools for optogenetics, new methods of super resolution microscopy etc.
- novel tools and instrumentation for thermogenetics (Fedotov et al, 2015; Safronov et al, 2015; Ermakova et al, 2017);
- a first application of a biosensor in subdiffraction microscopy (Mishina at al, 2015);
- SypHer2, a genetically encoded pH sensor allowing synaptic pH imaging (Matlashov et al, 2015);
- development of the red fluorescent genetically encoded H2O2 sensor (Ermakova et al, 2014);
- development of genetically encoded H2O2 generation/detection system based on fusion of D-amino acid oxidase and HyPer (Matlashov et al, 2014);
- development of the genetically encoded fluorescent sensor for intracellular NAD+/NADH ratio (Bilan et al, 2014);
- development of HyPer-3, the high dynamic range and fast-responding H2O2 probe for ratiometric and lifetime imaging (Bilan et al, 2013);
- first records of H2O2 production by phagocytosing macrophages at the level of single cell (Mishina et al, 2013);
- discovery of polarized H2O2 production in the immunological synapse (Mishina et al, 2012)
- discovery of H2O2 microdomains in the cells stimulated with growth factors, the first direct demonstration of local H2O2 signaling (Mishina et al., 2011);
- development of HyPer-2, improved version of HyPer with expanded dynamic range (Markvicheva et al., 2011);
- development of HyPer, sensor for H2O2 (Belousov et al, 2006).
|Vsevolod Belousov, D.Scfirstname.lastname@example.org, |
|Nataliya Mishina, Ph.D.||s. r. email@example.com, |
|Kseniya Markvicheva, Ph.D.||s. r. f.|
|Ilya Kelmanson, Ph.D.||r. firstname.lastname@example.org|
|Marina Roshina||r. f.|
|Ksenia Shishova||j. r. f.|
|Ekaterina Potehina, Ph.D.||j. r. email@example.com|
|Yulia Bogdanova||PhD firstname.lastname@example.org|
|Alexander Ivanenko||PhD email@example.com, |
|Elena Fetisovafirstname.lastname@example.org, |
|Dina Bassemail@example.com, |
|Alexander Kostyuk||res. firstname.lastname@example.org, |
|Dmitry Bilan, Ph.D.||s. r. email@example.com|
|Yuliya Ermakova, Ph.D.||s. r. firstname.lastname@example.org|
|Elena Kudryavtseva, Ph.D.||r. email@example.com|
|Mikhail Matlashov||PhD firstname.lastname@example.org|
|Arina Shokhina||PhD email@example.com|
Chemogenetic model of cardiac failure (2018-12-01)
Researchers from Molecular technologies laboratory (IBCh) in collaboration with Harvard medical school scientists developed a novel model of cardiac dysfunction caused by oxidative stress. This model is based on chemogenetics principles — enzymatic production of reactive oxygen species (ROS), stimulated by an external chemical substrate, and visualised by transgenic ROS sensor HyPer. The study is supported by Russian science foundation and published in Nature Communications.
- (2018). Chemogenetic generation of hydrogen peroxide in the heart induces severe cardiac dysfunction. Nat Commun 9 (1), 4044
Genetically encoded fluorescent pH probe for precise monitoring of cellular biochemistry (2018-12-01)
This “molecular pH-meter” allows the quantitative measurement of pH in living systems of various complexity. Using genetic engineering methods, SypHer3s can be delivered into a living cell and, due to its high brightness, can be used in high-resolution microscopy: for example, for accurate observations of fluctuations in acidity in cells or even whole organisms — the article describes a first measurement of pH in various tissues of the zebrafish embryo.
In addition, SypHer3s helped to demonstrate the functional heterogeneity of mitochondria in different compartments of neurons. In the body of a neuron, mitochondria are inactive, while in synapses they begin to actively pump out protons from the matrix creating an electrochemical gradient necessary for the synthesis of ATP. It is convenient to monitor these processes using the pH probe directed to the mitochondria. According to Vsevolod Belousov, “it seems that different parts of the neuron get the energy in different ways: the body uses glycolysis, and synapses — oxidative phosphorylation”.
- (2018). SypHer3s: A genetically encoded fluorescent ratiometric probe with enhanced brightness and an improved dynamic range. Chem Commun (Camb) 54 (23), 2898–2901