Brain Map

February 22, 2021 5:30 PM

The AI world

public talk by Chris Boos, arago GmbH, Frankfurt, Germany

Chris Boos has a mission: empowering human potential, freeing up time for creativity and innovative thinking through artificial intelligence (AI). To that end, Chris founded arago in Germany in 1995, pushing existing boundaries in AI technology to build a general AI. Since then, Chris has led arago to become a key partner and driver for the established economy, positioning arago’s AI HIRO™ as a platform for companies to reinvent their business models in the digital age.

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liquid nitrogen

February 23, 2021 1:00 PM

High-resolution cryoEM of membrane protein complexes

by Werner Kühlbrandt, Max Planck Institute of Biophysics Frankfurt, Germany

Structural biology and molecular cell biology is currently undergoing a revolution, brought about by technical developments in electron cryo-microscopy (cryoEM). The "resolution revolution" in cryoEM is primarily due to a new generation of direct electron detectors and image processing programs. With these developments it is now possible to determine the detailed structures and molecular mechanisms of large and dynamic protein assemblies, in particular membrane proteins, that have been intractable for decades. Single-particle cryoEM of membrane protein complexes now routinely achieves 2-3 Å resolution, where all sidechains, cofactors and (in the case of membrane proteins) lipids, bound ions and even water molecules in a protein complex are visible. As an added bonus, cryoEM simultaneously records images of co-existing conformational states of a protein complex; the different conformations can be separated by image processing and put into a functional sequence. Using the same instruments, electron cryo-tomography (cryoET) can image macromolecular assemblies in their cellular or organellar environment at increasingly high resolution. We combine both approaches to investigate the structure and molecular mechanisms of energy-converting membrane protein complexes. CryoET of Mgm1 on lipid membranes indicates how this mechano-chemical GTPase may shape the mitochondrial cristae. CryoET of mitochondrial mem-branes indicates that the respiratory chain supercomplex is essentially conserved from plants to mammals. Single-particle cryoEM of complex I from Yarrowia lipolytica reveals bound substrates and lipids at 3.2 Å resolution. While the chloroplast ATP synthase is monomeric, all mitochondrial ATP synthases form dimers that assemble into long rows that induce local membrane curvature. Single-particle cryoEM of the chloroplast ATP synthase shows how the complex is turned off at night to prevent unproductive ATP hydrolysis. The 2.7 Å map of a mitochondrial ATP synthase dimer resolves 13 different rotary substates, providing unexpected new insights into the universal mechanism of ATP synthesis by rotary catalysis that drives most cellular processes.

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Teaser Lecture Meier-Schellersheim

February 24, 2021 1:00 PM

Aim for mechanistic models!

by Martin Meier-Schellersheim, National Institute of Allergy and Infectious Diseases (NIAID), Bethesda, USA

Theoretical modeling in cell biology has to strike a balance between finding parsimonious, manageable models with not too many parameters or assumptions that are not directly accessible to experimentation on one hand and, on the other hand, not suggesting models that are regarded as too simplistic and biologically unrealistic. During the search for such balance, it is frequently overlooked that concise models implicitly make many assumptions without actually exposing them to scrutiny. In my talk, I will illustrate this issue using computational models of simple signaling pathways and show how detailed mechanistic models of intracellular reaction networks can be explored efficiently. We combine both approaches to investigate the structure and molecular mechanisms of energy-converting membrane protein complexes. CryoET of Mgm1 on lipid membranes indicates how this mechano-chemical GTPase may shape the mitochondrial cristae. CryoET of mitochondrial mem-branes indicates that the respiratory chain supercomplex is essentially conserved from plants to mammals. Single-particle cryoEM of complex I from Yarrowia lipolytica reveals bound substrates and lipids at 3.2 Å resolution. While the chloroplast ATP synthase is monomeric, all mitochondrial ATP synthases form dimers that assemble into long rows that induce local membrane curvature. Single-particle cryoEM of the chloroplast ATP synthase shows how the complex is turned off at night to prevent unproductive ATP hydrolysis. The 2.7 Å map of a mitochondrial ATP synthase dimer resolves 13 different rotary substates, providing unexpected new insights into the universal mechanism of ATP synthesis by rotary catalysis that drives most cellular processes.

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Teaser Lecture Südhof

February 25, 2021 5:00 PM

Molecular codes enabling brain function

by Thomas Südhof, Stanford University, USA

For a person to think, act, or feel, the neurons in a person’s brain must communicate continuously, rapidly, and repeatedly. This communication occurs at synapses, specialized junctions between neurons that transfer and compute information on a millisecond timescale. By forming synapses with each other, neurons are organized into vast overlapping neural circuits. As intercellular junctions, synapses are asymmetric with a presynaptic terminal that emits a transmitter signal and a postsynaptic cell that receives this signal. Synapses differ in properties and exhibit distinct types of plasticity, enabling fast information processing as well as learning and memory. Synapses are the most vulnerable component of the brain whose dysfunction initiates multifarious brain disorders. Despite their importance, however, synapses are poorly understood beyond basic principles. Thomas Südhof’s laboratory studies how synapses form in the brain and how their properties are specified, which together organize neural circuits. Moreover, the Südhof laboratory examines how synapses become dysfunctional in neurodegenerative and neuropsychiatric disorders to pave the way for better therapies.

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