What do the cytoskeleton and a tent have in common? Interview with Philip Bleicher

Philip Bleicher is a PhD candidate in his final year of studies at the Technical University of Munich. I got to know Philip during my time working in the same department and over time he became an invaluable lunch companion and a great friend. For the first of my blog posts for a while, I have decided to go for something a little bit different. The first of a new format. I plan to publish a series of interviews with scientists, researchers and engineers who I have been fortunate enough to meet throughout my working life. My goal is to ask them to explain what they do (in this case with some interesting tent metaphors), what motivates them, and how they got where they are today. 

Important side note. Philip just had a paper published where he was able to demonstrate a minimal system which shows how several different proteins interact to regulate the cellular cytoskeleton. Check it out here: https://www.nature.com/articles/s41598-020-62942-8

KT: Tell me a bit about yourself - how would you describe yourself?

PB: I am a person with an attention span that is too short for this question but enough enthusiasm for science to make up for it

KT: Haha, ok, so then tell me about you and science - what is it that you are currently working on?

PB: My research is focused on the reconstitution of the cytoskeleton. Our approach includes the isolation of individual components that make up cells and the cytoskeleton, like structural proteins and their interaction partners. Specifically, I work with actin and its binding proteins. Actin is particularly interesting among the structural proteins as it has the ability to form networks that give stability to the cell, as well as being highly dynamic. I try to contribute something to our understanding of these (seemingly) contradictory properties.

KT: So can I understand the cytoskeleton as a kind of structural framework, like the poles and ropes holding up a tent - except that the poles and ropes can grow and shrink? Can you think of a better analogy?

PB: I think that’s a pretty good analogy. Now of course the cell can only use materials it can build and deconstruct on its own. This is why actin is such a cool protein, it initially exists as a monomer that can spontaneously polymerize into filaments by self-association. Individual filaments can buckle and fluctuate a lot, but  they can be bundled to create more rigid structures, like so called stress fibers. Alternatively, filaments can be severed into fragments or even be depolymerized back to monomers, or they associate with motor proteins that can pull on fibers to change the shape of the cell, or transport cargo along the cytoskeleton like trains that use the poles of the tent as tracks.

Now imagine you would want to make the tent crawl around without losing the attachment to the ground (there is a storm now that would blow your tent away, I forgot to mention that). You would need to constantly relocate the anchoring points to the ground, while rearranging the poles and ropes in the tent in a way that allows you to soften the wall that you want to push forward. Simultaneously you’d have to drag the back of the tent with you. To be able to move in such a way, you would need to be able to control the stability, forces and flows along your poles and ropes and adjust them to meet the demands depending on where in the tent you are – and where you want your tent to go. Okay, enough talk about the tent, the point is: The cytoskeleton is able to do all that and we are trying to understand all the details about these fascinating processes. It is challenging on a biochemical level, because so many proteins are involved, but also from a physical point of view. Remarkably, new discoveries in reconstitution or cell biological experiments and their implementation in physical models has proven to be a quite insightful strategy in the field.

KT: What a great explanation - I feel like I can really visualise what you mean. I can see why you're so fascinated by learning how to understand the cytoskeleton - it seems like a remarkable system with many open questions still remaining. Where do you think this field is going next? 

PB: I think two developments are taking place that will sooner or later advance the field in the next era. On the one hand, imaging techniques get better and allow us to resolve even smaller structures. One of the big advantages of reconstituted systems is that we can really resolve individual filaments without the noisy background of the cell. I hope this will become obsolete eventually. On the other hand, minimal reconstituted system become more and more complex. Recently there was a paper published where they managed to reconstitute photosynthesis in a lipid vesicle which really blew my mind*. I wouldn’t be surprised if we can soon implement gene signaling in artificial cells or other signaling cascades to trigger responses like actin polymerization. Then the vesicle would be truly self regulated on a biological level. Although we have shown in several publications how active matter is self-organizing even without signalling (by switching genes on or off)**. This is particularly interesting  and important for our understanding of fundamental processes in cells.

KT: I can’t wait to see where this field ends up in the coming years - certainly worth keeping an eye on.  Thank you for taking the time to answer my questions!

*reference to the paper that blew Philip’s mind (which is behind a paywall unfortunately): https://www.nature.com/articles/nbt.4140?platform=oscar&draft=collection 

**reference for one of the publications that Philip is referring to: https://science.sciencemag.org/content/345/6201/1135.abstract