Dr. Opatowsky's Lab
Head - Structural Biology Lab
Dr. Yarden Opatowsky, a structural biologist and senior lecturer in the Mina and Everard Goodman Faculty of Life Sciences, is a returning scientist from Yale University.
Opatowsky's interests include structural aspects in neurobiology, cancer research and microorganisms pathogenesis.
Opatowsky's team uses X-ray crystallography in combination with single particle electron microscopy as well as other biochemical and biophysical methods to elucidate protein–protein and protein–membrane interactions that are critical to the function of the investigated biological systems.
Taking advantage of X-ray crystallography’s ability to capture pictures of biologically significant processes at the atomic level, Opatowsky shows the exact molecular underpinnings of signaling and pathogenic events.
Fitting the crystal structures of smaller fragments into larger 3D electron microscopy reconstructions, allows a more comprehensive structural and mechanistic understanding of the investigated biological system.
Infectious diseases are, and will continue to pose a major threat to human health. As pathogens develop ways to avoid elimination by antibiotics, there is an urgent need to modify and improve existing drugs, and to identify new drug targets.
Dr. Opatowsky's research is concerned with two such pathogens: the Human Cytomegalovirus (HCMV), a major cause for congenital neurodevelopment diseases, and Pseudomonas aeruginosa(PA), which can lead to respiratory failure and death in cystic fibrosis (CF) patients. By characterizing the tertiary and quaternary structural architecture of the invasion and survival machineries of these pathogens, the research team hopes to discover a "crack in armor" that will enable the development of a new line of drugs to fight HCMV and PA infections and related diseases.
Cell Signaling and Cancer Research
Growth factors activate receptors to initiate precise signaling events across the cell membrane. Research is focused on understanding how the extracellular event of ligand binding to the receptor is translated into an accurate intracellular response.
Opatowsky's team uses structural investigations of coordinated signaling through assemblies of Receptor Tyrosine Kinases (RTKs) and co-receptors. Through the parallel use of X-ray crystallography and single-particle electron microscopy, basic mechanistic questions concerning the early stages of cell signaling can be addressed. Opatowsky studies key signaling processes in the formation of cancerous tumors. Signaling via receptors plays a pivotal role in the control of cellular processes such as cell adhesion, migration, survival and proliferation.
In cancer, the complex signaling networks are hijacked to make cells proliferate. The receptor is, therefore, the first point where the malignant message can be intercepted. Opatowsky's research focuses on the RTK receptors and the structural understanding of its stimulation and signaling mechanisms, using x-ray crystallography and electron microscopy. By understanding the stimulation and signaling mechanisms of the RTK receptors, Opatowsky hopes it will be possible to intercept, decipher and block the molecular signals which cause abnormal cell growth and proliferation.
Axon Guidance and Neurodegenerative Diseases
The accurate formation of neuronal networks during development is crucial for brain function and is controlled by axon attractive and repulsive cues. In most cases, extracellular guidance factors activate cell-surface receptors, which are presented on the tips of the navigating axons. Consistent with the central role that these receptors have in developmental neurobiology, recent advanced genomic studies correlates several of these guidance factors with pathological conditions of the nervous system, such as Parkinson's disease, schizophrenia, autism, dyslexia and more.
Opatowsky's research aims at gaining a mechanistic understanding of axon guidance receptors and the downstream signaling pathways that they trigger.
Looking to the Future
Dr. Opatowsky intends to pursue the incorporation of x-ray crystallography and electron microscopy as complementary techniques for the conduction of a dynamic structural research of multipart signaling complexes.