I graduated from the Moscow Institute of Physics and Technology (Phystech) with MSc in biophysics in the days when biophysics was mostly associated with electrophysiology of ion channels and structure of proteins and nucleic acids. Since I was fascinated with nonlinear dynamics and pattern formation I went on to do my PhD in the theoretical chemistry group of Prof. Ray Kapral in the University of Toronto, Canada. My career path took me into several countries and working environments, however my ultimate goal has always been understanding complex self-organized behavior of biological systems. In 2006 I joined the University of Edinburgh where I am presently a Professor of Computational Cell Biology.
For the main directions of current pursuits in our group, please see the Research page. Here I briefly outline other areas of interest and past research exploits.
In the late 1990s, a gold rush of functional genomics swept the globe. I could not resist the temptation of its promise to reveal the inner workings of gene regulatory networks and joined one of the first in Canada microarray facilities then just established in the Toronto-based Princess Margaret Hospital. Trying to bring quantitative methodology into microarray data analysis, I focused on identifying various sources of systematic errors and estimation of random noise throughout the technology pipeline from array printing to image analysis. What came out of this effort was one of the first quantitative models of the fluorescence intensity ratios reported by this method and a set of practical methods allowing inference of the best approximation for the true gene expression ratios hidden within the experimental measurements. Some of these methods were later implemented within commercial software during my industrial stint with GeneData AG in Basel, Switzerland.
B. Schimmer, M. Cordova, H. Cheng, A. Tsao, A. Goryachev, A. Schimmer, Q. Morris, Global profiles of gene expression induced by ACTH in Y1 mouse adrenal cells. Endocrinology, 147(5), 2357 – 2367 (2006).
L. Chen, A. Goryachev, J. Sun, P. Kim, H. Zhang, M. Phillips, P. Macgregor, S. Lebel, A. Edwards, and K. Furuya, Altered expression of genes involved in hepatic morphogenesis and fibrogenesis are identified by cDNA microarray analysis in biliary atresia. Hepatology. 38(3), 567 - 576 (2003).
My strong belief in the predictive power of computational modeling dates back to my PhD days in the group of Ray Kapral at the University of Toronto. My research question was to find out if any new or unusual patterns existed in spatially-distributed systems (“media” in chemical terms) capable of complex-periodic oscillations. The notion of complex periodicity is best exemplified by the phenomenon of period-doubling. Imagine that you start with a time series describing normal periodic oscillation and then slightly increase the amplitude of every second maximum while reduce that of each previous. As a result, new oscillation pattern will repeat itself with the twice longer period. Viewed in a 3D space, such an oscillation will look not like a typical simple ring but rather as a twice-folded onto itself structure (mathematicians call it a “braid”) on which an imaginary walking observer would have to make not one (2pi) but two full turns (4pi) until he would come to the same point. We were particularly interested if such complex-periodic systems could exhibit spiral waves that are common for physical and biological systems with simple periodic dynamics. To our complete surprise, it turned out that in the period-2 system, an attempt to form a simple one-armed spiral wave inevitably results in the creation of a new, not yet reported then in the literature, structure, which we called a synchronization defect line . This is because across this line, the phase of the oscillation changes by a quantum of 2pi so that the circular walk around the spiral center amounts to the full 4pi phase increment, to match the longer period of the period-2 oscillation! Moreover, spiral waves are not necessary to have synchronization defect lines, simply, without spiral waves, these lines have to be circular demarkating the domains with oscillation phase shifted by 2pi. Further, I demonstrated that synchronization defect lines can also exist in excitable systems exhibiting complex periodicity (yes, such systems also exist, see below).
Does this phenomenon have anything to do with biology? It turned out, yes! Cardiologists have long known about the existence of alternating heart beats, one longer, one shorter (and smaller in amplitude). These so-called alternans formally are a period-2 complex excitable behavior. Discordant alternans, when at the same time moment in one heart location the beat is longer and in another location it is shorter, were also found with mto expoving electrodes. Thus, we suspected that synchronization defect lines should exist in the heart, but with the technology of those days their observation was, alas, impossible. Shortly after the publication of my PhD thesis that was based solely on modeling results, synchronization defect lines were observed by several experimental groups first in chemical and then biological systems. Finally, the technology of spatial optical mapping with voltage and Ca-sensitive dies allowed to observe synchronization defect lines in experiments with whole perfused animal hearts!