PhD (Moscow State University)
Research Areas: Cell Biology, Cytometry, Bioanalytical Chemistry
We are an interdisciplinary team that uses advanced bioanalytical methods to study the molecular mechanisms of biological processes at the single cell level. Such studies are necessary to understand the processes that generate heterogeneous cell populations, e.g. embryogenesis, tumorigenesis, tissue regeneration, and neurodegeneration. Among our tools is chemical cytometry, a new bioanalytical technique that utilizes capillary electrophoresis with laser-induced fluorescence detection in order to study the chemical contents of single cells [1, 2]. Combining chemical cytometry with different types of microscopy allows us to probe individual cells for their chemical contents and biological status simultaneously, which is necessary to understand the molecular mechanisms of the processes governing the cells’ fate . We have been able to monitor both metabolism and protein expression in single cells by means of chemical cytometry [3, 4].
Currently, we have three ongoing projects. The first one deals with elucidating the molecular mechanism of Alzheimer’s disease. We aim at finding the initial molecular damage that is responsible for the formation of neurofibrillary tangles in individual neurons. Our working hypothesis assumes that abnormal splicing of tau protein (microtubule-associated protein expressed in neurons) is to be blamed for this pathology. We intend to compare alternative splicing of tau protein in individual normal and disease-affected neurons through developing appropriate chemical cytometry methods.
The second project focuses on the study of the molecular mechanisms that govern asymmetric proliferation and differentiation of stem cells. Recent success in controlling stem cell differentiation opens an exciting possibility of curing a number of presently incurable disorders such as cardiovascular diseases, autoimmune diseases, diabetes, osteoporosis, cancer, Alzheimer's disease, Parkinson's disease, severe burns, spinal cord injuries and birth defects. Due to their complex patterns, proliferation and differentiation of stem cells have to be studied at the single cell level. We are using chemical cytometry combined with time-lapse microscopy to elucidate the differences in chemical contents between asymmetric daughters of stem cells.
The third project deals with developing high-throughput instrumentation and methods for chemical cytometry as well as chemical cytometry combined with confocal microscopy.
Krylov, S.N.; Zhang, Z.; Chan, N.W.C.; Arriaga, E.; Palcic, M.M.; Dovichi, N.J. Correlating cell cycle with metabolism in single cells: combination of image and metabolic cytometry. Cytometry 1999, 37, 14-20.