Dr. Alexey Kuznetsov: Research
My central professional goal is to establish interdisciplinary research that combines experimental and theoretical biology with mathematical and statistical modeling. I am an applied mathematician by training. My dissertation addressed phenomena of synchronization and pattern formation in active, oscillatory networks using qualitative theory of differential equations and computational modeling. In addition to mathematics, I learned biophysics and molecular biology during my postdoctoral training. This cross-disciplinary background has proven to be a significant advantage in seeking explanations to biological problems via mathematical and computational modeling. In the future, I want to connect different levels of biological research, from molecular and cellular to system and behavioral, focusing on medical and pharmaceutical problems and further developing my experimental and medical collaborations.
One of my main research projects is study of firing properties of the midbrain dopaminergic (DA) neuron and signal processing performed by this cell. The work has been initiated in collaboration with an experimentalist Charles Wilson (UTSA, Biology Department) and Nancy Kopell (BU, Mathematics Department) (Kuznetsov et al., J Neurophys 2006). The central dopamine system has been suggested to be involved with many behavioral and cognitive tasks. Dopamine neurotransmission has been found responsible for addictive behavior and is impaired in psychiatric disorders. However, a combination of experimental and modeling studies has not given a consistent picture of the DA neuron input-output relation (see Kuznetsov et al., Scholarpedia 2007 for discussion). Therefore, the role of the dopaminergic neuron and the role of dopamine itself are topics for active investigations for neuroscientists, pharmacists and physicians.
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Another major field of my research interest is self-sustained oscillatory dynamics of protein expression. Most well known robust oscillatory circuits in molecular biology are the circadian clock and the cell cycle engine. Recently, other examples of such circuits have been discovered in many other regulatory processes, such as apoptosis, metabolism and morphogenesis. A question addressed in many recent studies is how specific are these oscillatory circuits and their elements. Experimentally this problem is investigated in the Applied Biodynamics Laboratory headed by James Collins at the Biomedical Engineering Department, BU. In close collaboration with an experimentalist Mads Kaern from the above laboratory, I have constructed a robust, hysteresis-based genetic relaxation oscillator and provided a theoretical analysis of the conditions necessary for single-cell oscillations (Kuznetsov et al., SIAM Appl. Math. 2004). Based on my analysis, I have proposed a modification in the architecture of the gene regulatory network that has substantially increased robustness of the oscillations.
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