Virtual Agenda

Alberto Bartesaghi received his B.Sc. and M.Sc. from the Department of Electrical Engineering at the Universidad de la Republica, Montevideo, Uruguay, and his Ph.D. from the Department of Electrical and Computer Engineering at the University of Minnesota, Minneapolis, MN. In 2005, he joined the Biophysics Section of the Laboratory of Cell Biology at the NCI/NIH, Bethesda, MD to conduct his post-doctoral studies, and later became an Associate Scientist with the Center for Cancer Research. Dr. Bartesaghi received the “Norman P. Salzman Memorial Award in Virology” from the Foundation for the National Institutes of Health, Bethesda, MD for his work on the molecular architecture of native HIV-1 gp120 trimers. In 2018, he joined the Departments of Computer Science and Biochemistry at Duke University as an Associate Professor. Dr. Bartesaghi is a pioneer in the development of computational methods for solving structures of large macromolecular complexes by single particle cryo-EM, cryo-electron tomography and subvolume averaging. He solved many influential high-resolution structures including those of DNA-targeting CRISPR/Cas9 surveillance complexes, G-protein coupled receptors (GPCRs), the human cancer target p97, membrane transporters and channels involved in signaling and metabolism, and envelope viral glycoproteins including SIV, HIV1, Influenza and Ebola. He is also interested more broadly in data science, machine learning, computer vision, and molecular computational imaging.

Cryogenic electron microscopes allow researchers to peer at the microscopic shape of proteins like never before. These machines blast proteins with a 300,000-volt beam of electrons so that highly sensitive detectors underneath can tease out their shapes based on the interaction with the sample. Recognizing protein structure and function is essential for scientists trying to design better drugs to tackle some the world’s most devastating diseases, including HIV, cancer and Alzheimer’s disease. High energy electrons, however, are extremely damaging to proteins and to help protect the samples in the microscope, researchers cryogenically freeze them to help maintain their integrity and use very low electron doses to prevent structural damage. This allows the recording of images of intact proteins and biomolecular structures that were previously 22 FIP 2020 Annual Symposium Duke Speakers inaccessible to other technologies. Modern electron detectors can record rapid bursts of frames (up to 1,500 frames per second), allowing the capture of individual electron events during the exposure and resulting in extremely low signal-to-noise ratio images. Recent advances in computational imaging have allowed the correction of the naturally occurring drift of the biological sample during the exposure -caused by beaminduced motion- dramatically improving image resolution and allowing the visualization of the 3D shape of complex molecular machines at unprecedented levels of detail. These technological advances have turned cryo-EM into a powerful tool for biological discovery and structure-based drug design. training, telemedicine and more.