Ph.D.: Weizmann Institute of Science, Israel

Post-doctorate: Max-Planck-Institute for Biochemistry, Germany

Position: Senior Lecturer

Department of Life Sciences

Faculty of Natural Sciences

E-mail: omedalia@bgu.ac.il

Webpage:http://cmsprod.bgu.ac.il/Eng/Teva/departments/LifeScience/FacultyMembers/Ohad_Medalia.htm

Applied uses of electron tomography

Background

Improvements in electron microscopy, in conjunction with advances in computercontrolled systems, now allow for investigation of biological specimens at sub-critical dose exposure, thereby minimizing beam-induced radiation damage to negligible levels. The development of cryo-electron microscopy ensures “close-to-life” preparation by vitrification, even for biological samples as large as intact organelles and cells. Since neither fixation nor staining is required, vitrification maintains the integrity of a cell and causes almost no artifacts. Thus, vitrification allows cells to be arrested in various functional states. Indeed, electron tomography of ice-embedded specimens is the only methodology that allows retrieval of 3-D structural information from large polymorphic structures, such as intact cells and organelles, at a resolution of 4-6 nm. Although tomograms of intact cells cannot be enhanced using averaging procedures, they exhibit a sufficient signal to noise ratio to allow segmentation and comparison of macromolecular complexes in situ. As such, cryo-electron tomography can be a useful tool in medical research and drug discovery processes.

Current research

1. Electron tomography and drug discovery – Individual proteins and macromolecular complexes can be detected in 3-D by electron tomography. By using labeled drug candidates (lead compounds), the specificity as well as the affinities of a drug inside a cell could be resolved in situ. For example, observation and monitoring of drug-antigen interactions in living cells can be detected and visualized at early stages of the drug development process, at relatively low costs. We are developing strategies for labeling drugs in order to resolve their network of interactions within cells.
2. Structural analysis of integrin-mediated cell adhesion – Cell adhesions play an important role in the organization, growth, maturation, and function of living cells. The interaction of cells with the extracellular matrix also plays an essential role in a variety of disease states, including tumour formation and metastasis, inflammation and repair of wounded tissues. The structure of the machinery involved remains, however, unknown. By understanding the structure of these macromolecular assemblies we will be able to suggest new approaches for inhibiting cell adhesion.
3. Structural analysis of the nuclear lamina – Forming a boundary between the nucleus and the cytoplasm, the nuclear envelope consists of two concentric membranes (outer and inner) connected at nuclear pores and an underlying lamina, a network-like scaffold structure providing mechanical stability for the nucleus, cell and tissue. As the main structural constituents of the nuclear lamina, lamins are also present in the nucleoplasm. These proteins are members of the intermediate filament (IF) protein superfamily and are probably the ancestors of all IF proteins. Point mutations in lamin proteins cause a set of diseases recently detected in the elderly. As such, we are presently addressing the structure of the nuclear lamina.

Selected publications