Laboratory of Genetics
Biological life is organized along a continuum that ranges from complete living organisms down to tissues, cells, cellular organelles, large “macromolecular” assemblies composed of proteins and nucleic acids, small “molecular” assemblies or individual molecules, and finally, atoms and subatomic particles. Since the advent of light microscopy several centuries ago, researchers have been unraveling the connection between biological structure and function along this continuum at increasingly finer degrees of spatial resolution. As technology improves, many researchers are finding that directly visualizing the structure of individual macromolecules or their assemblies at resolutions nearing the level of individual atoms can better reveal various types of dysfunction that lead to disease.
Dmitry Lyumkis utilizes and develops cutting-edge transmission cryo-electron microscopy (cryo-EM) techniques to understand the biological complexity characterized by large macromolecules and their assemblies. By observing previously unseen molecular structures under different physiological conditions and at resolutions truly approaching atomic, Lyumkis aims to understand and interconnect the complex roles macromolecules play in human diseases such as cancer and HIV.
Lyumkis determined structures of macromolecular assemblies called “intasomes” from viruses including and related to HIV, which allows them to establish permanent infection in target host cells. These structures further our understanding of the molecular hallmarks of infection and, importantly, provide direct chemical blueprints for improving antiviral therapies used to treat HIV-infected individuals.
Lyumkis developed new methods to quantitatively evaluate and experimentally improve anisotropic (directionally dependent) resolution in cryo-EM, which frequently plagues attempts to derive meaningful structural information from biological samples. The techniques were shown to yield higher quality data and have broad applicability to structure determination and evaluation.
Lyumkis used cryo-EM and complementary computational tools to decipher some of the key molecular steps for how ribosomes (structures that build proteins) assemble into an intricate, albeit highly ordered amalgamation of protein and RNA constituents. His lab is actively developing methods for generalizing the techniques and applying them to increasingly complex and dynamic assemblies of ribosomes and other macromolecular machines.