Dr. Makhatadze completed his postdoctoral work at the Department of Biology at Johns Hopkins University before moving to his first faculty position in the Department of Chemistry and Biochemistry at Texas Tech University. After three years at Texas Tech, he moved to the Penn State University College of Medicine, where he was Professor at the Department of Biochemistry and Molecular Biology and directed a graduate program in Chemical Biology. Dr. Makhatadze joined Rensselaer in 2007 as a Constellation Professor in Biocomputation and Bioinformatics. He is a member of the American Chemical Society, the American Society for Biochemistry and Molecular Biology, the Biophysical Society, the Federation of American Societies for Experimental Biology, and the Protein Society. He is an elected fellow of the American Association for the Advancement of Science (AAAS) and has served on the editorial boards for the Biochemica et Biophysica Acta, the Biophysical Journal, and the Journal of Biological Chemistry. Dr. Makhatadze is currently serving on the editorial boards of the Frontiers in Molecular Biosciences: Protein Folding, Misfolding and Degradation, PROTEINS: Structure, Function, and Bioinformatics and Protein Engineering, Design and Selection. He is also a past and present member of the scientific review committees for the National Institutes of Health (NIH) and the National Science Foundation (NSF). Dr. Makhatadze has mentored more than 20 PhD students, who have gone on to achieve prominent positions in both academia and industry.
Ph.D. Moscow Institute of Physics and Technology and Institute of Protein Research, 1991 - Biochemistry and Biophysics
B.S. Georgia State University, 1985 - Physics/Biophysics
Postdoctoral Research & Training
Postdoctoral Researcher, Johns Hopkins University, 1993-1995 - Biology
Research in the laboratory is directed towards understanding the structural and thermodynamic basis of the contributions of individual molecular components to the functional dynamics of macromolecular complexes. In order to probe the role of different interactions in protein folding, stability and protein interactions with the ligands (ions, proteins, DNA, RNA, small effectors), a variety of experimental techniques as well as computational methods of analysis are used. Recombinant DNA technology is used to incorporate different amino acid residues into a given position in a protein sequence. The effect of these mutations on the overall energetics, structure and function of proteins is measured under different conditions such as salt concentration and ion type, temperature, and pH. Experimental techniques assessing energetics include scanning calorimetry, pressure-perturbation calorimetry, titration calorimetry, circular dichroism spectroscopy, fluorescence spectroscopy, stopped-flow kinetics, and analytical ultracentrifugation. Structural information on the systems is obtained using multidimensional NMR spectroscopy. Computer simulations are used to obtain atomistic details for individual model systems, and analyzed using AI and ML enhanced tools.
Two main projects are under development in the laboratory.
The first project studies physico-chemical basis of adaptation of organisms to high hydrostatic pressure at the level of individual macromolecules. Pressure is an important environmental variable that plays an essential role in biological adaptation for many extremophilic organisms, so called piezophiles. On Earth these organisms are generally populating the deep ocean floor where hydrostatic pressure can reach 110 MPa (~1,100 atm). Single cell organisms are not the only ones evolved to live under high hydrostatic pressure. The segmented microscopic animals tardigrades (“water bear”) can survive pressures up to 6,000 atm in the dormant state. Pompeii worms (Alvinella pompejana) are species of polychaete worms that live at high pressure and temperature near hydrothermal vents on the ocean floor. More recently, several species of nematoda were identified in the deep terrestrial subsurfaces. Bacterial species have been isolated from 1,350 meters into the Earth crust where temperature reaches 102°C and pressure is estimated to be in excess of 3,000 atm. There are also reports of prokaryotic organisms at the bottom of the oil well sediments and deep in the Arctic ice. All these examples suggest the possibility of life forms on other planets even though the temperature and pressure conditions can be dramatically different from those on the surface of Earth. Such different temperature and pressure conditions are expected to be found under the ice crust on Mars, Jupiter's moon Europa, and Saturn's moon Enceladus. Using a novel method of pressure-perturbation calorimetry combined with protein engineering methods, detailed computer simulations, and AI/ML driven bioinformatics we are deciphering the role of different interactions in defining structural and functional state of proteins at high hydrostatic pressure.
The second project deals with the mechanisms by amyloid fibrils formation using GFP as a molecular sensor. Insoluble protein aggregates called amyloid fibrils are linked to various human diseases such as Alzheimer’s disease, Parkinson’s disease, and type II diabetes. Our research demonstrates that regardless of their amino acid sequence, green fluorescent protein (GFP) can bind the core of amyloid fibrils. The interaction between GFP and amyloid fibrils is specific, as GFP does not interact to the monomeric forms of these peptides/proteins or other protein aggregates. GFP cannot bind to amyloid fibrils formed by large proteins that have a fuzzy coat surrounding the amyloid core. However, if protease digestion removes the fuzzy coat, GFP can detect the amyloid core of these fibrils. By using NMR, we have mapped the binding interface on GFP and validated it through mutagenesis. We proposed a FRET-based sensor for amyloid detection based on GFP's ability to bind amyloid fibrils for practical applications. We use a battery of biophysical methods (ThT fluorescence, circular dichroisms and deep-UV resonance Raman spectroscopies, NMR, analytical ultracentrifugation, small angle X-ray scattering, hydrogen-deuterium exchange mass spectrometry), biochemical methods (protease protection, bacterial expression, isotopic labeling), and computational method (replica-exchange molecular dynamic simulations) to identify key elements that are involved in the amyloid structure formation. The ultimate goal is to develop inhibitors that modify the fibrillation pathways.
Rational design of protein for thermostability, functional protein dynamics, protein-protein and protein-ligand interactions, mechanism of adaptations to extreme conditions (thermophiles, psychrophiles, halophiles, piezophiles), bioinformatics, computer simulations of protein energy landscapes
BIOL 4760 - Molecular Biochemistry I
Part I of a two-semester sequence focusing on the chemistry, structure, and function of biological molecules, macromolecules, and systems. Topics covered include protein and nucleic acid structure, enzymology, mechanisms of catalysis, regulation, lipids and membranes, carbohydrates, bioenergetics, and carbohydrate metabolism.
The following is a selection of recent publications in Scopus. George Makhatadze has 144 indexed publications in the subjects of Biochemistry, Genetics and Molecular Biology, Chemistry, Medicine.