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Benjamin Engel - deciphering the function of cellular architecture

Benjamin Engel © Helmholtz Zentrum München/Carolin Jacklin

Dr. Benjamin Engel combines “structural cell biology” with more traditional biology approaches, including biochemistry and proteomics for molecular identification, genetics to tease apart molecular mechanism, as well as live-cell light microscopy to capture dynamic cellular events that enable him to decipher the function of cellular architecture.

Starting from autumn 2019, Benjamin Engel will run his independent lab at the Helmholtz Pioneer Campus at the Helmholtz Zentrum München.

In this interview, he shares his motivation and future ambitions.

 

What is your main scientific aspiration?

I am fascinated by the beautiful complexity of cellular architecture. Cells orchestrate their many biochemical reactions by concentrating specific molecules together within subcompartments called organelles. These organelles include classical membrane-bound compartments such as the nucleus, ER, and Golgi, endosymbiotic compartments such as energy-producing mitochondria and chloroplasts, as well as large cytoskeletal assemblies such as centrioles and cilia. More recently, it has been discovered that cells assemble a diverse variety of dynamic, non-membrane-bound organelles, which compartmentalize specific macromolecules together through a process called liquid-liquid phase separation.

My group investigates the interrelationship between the form of the organelle and the function of its resident macromolecules. We seek to understand how organelle architecture directs molecular function, and reciprocally, how macromolecules sculpt and shape organelles. While we are broadly interested in all organelles, we are currently focusing on the cilium and the chloroplast— two compartments with dramatic structure-function relationships. The cilium is a “cellular antenna”, which extends from nearly every cell of the human body and performs a variety of signaling functions that are crucial to human health. The chloroplast uses its intricate architecture to direct photosynthesis, transforming sunlight into the chemical energy of life while removing carbon dioxide from the atmosphere and replacing it with oxygen. We are particularly interested in understanding how the molecular architecture of the chloroplast is affected by environmental stresses caused by climate change.

Why did you choose to join the HPC? 

One attractive aspect of joining the HPC is having the resources and freedom to immediately assemble my group and dive headfirst into our research, with few other obligations. The research mission of “Environmental Health” encourages me to pursue a diverse range of important topics, from the cell biology of human health to the effects of climate change on photosynthetic organisms. Embedding my group within the Helmholtz community allows us to interact with experts in complementary techniques that will enrich our research, including next-generation sequencing, proteomics, microfluidics, machine learning, and a variety of structural approaches. In particular, my HPC colleagues are a major asset because we all come from different fields, providing rich opportunities to learn and collaborate on innovative new directions. More broadly, Munich offers me a vibrant local research community, with colleagues and collaborators at TUM, LMU, and the Max Planck Institute.

How are you planning to answer your scientific questions? 

We aim to chart the molecular landscapes of organelles by combining high-resolution structural analysis with precise cellular localization. My group’s favorite technique is cryo-electron tomography, which we use to directly visualize macromolecules “in situ”, within the native cellular environment. First, we rapidly freeze the cells in non-crystalline vitreous ice, preserving them in a state of suspended animation. Next, we use a focused ion beam to thin the cells, followed by cryo-electron tomography to acquire 3D images (called tomograms) of the native cellular interior with molecular resolution. These tomograms enable us to solve molecular structures directly within the cell, at sufficient resolution to distinguish different conformational states and interaction partners. We then map these structures back into the cellular volume with nanometer precision, allowing us to analyze molecular organization within the cell at the scale of single molecules. To gain more functional insights, we combine this “structural cell biology” with more traditional biology approaches, including biochemistry and proteomics for molecular identification, genetics to tease apart molecular mechanism, as well as live-cell light microscopy to capture dynamic cellular events that we correlate with our tomograms. We also use single particle cryo-electron microscopy to generate near-atomic-resolution structures of isolated macromolecules, which can then be mapped into the cellular structures, bridging the scales from atoms to cells.

Which are your interests beside research?

When not exploring the inner universe of the cell, I like to explore the world around me. My wife and I have a shared passion for travel, and I am actually answering these questions while visiting our 52nd country together. Our two boys have not slowed us down— they are always up for adventure, and it is exciting to see how much they take from our travels. It is invigorating to see new places and learn about new cultures. I also think it is very important, especially in these challenging times when some groups are turning inwards instead of joining together to work on global challenges such as climate change. Experiencing other cultures first hand allows us to see that we should celebrate our differences but also embrace our shared humanity. We are all citizens of the Earth, first. When not traveling, I love to spend the day outside in nature with my family. We often go to the Englischer Garten, the Isar river, one of Munich’s many clean lakes or fantastic public pools, or the Alps for an easy daytrip. Munich is a relaxing green home, the perfect place to raise a family, and a very well-connected home base for exploring the rest of the world.

 

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