Interview with Dr. Yuval Elani – ‘The cell membrane is more than just a capsule’

Dr. Yuval Elani is Group Leader at Imperial College, UK, in the department of Chemical Engineering. He and his team of about 20 scientists work in the field of bio-inspired technology, which means taking inspiration from biological systems and concepts to build new types of technologies.

In the interview he tells us a bit more about his recent research on membranes, one of his recent projects on dynamic compartmentalization, and the main challenges in developing applications.

Can you tell me a little bit about yourself?

I grew up in South Africa, Israel, and London but I did my undergraduate studies at Cambridge University. After my PhD at Imperial College, I established my group through a series of fellowships, including a UKRI Future Leaders Fellowship, which allows me to work for the next seven years in the field of synthetic cells.

What are you and your team working on?

One of the areas in which my team specializes is the design of functional biological membranes. Most of the functions of existing synthetic cells[1] are performed by proteins or active components while membranes are passive elements. For us, the membrane is more than just a capsule. We design new types of membranes so that they are an integral part of the design elements of our cells. We can introduce all sorts of interesting behaviors into our synthetic cells[1] using principles of membrane engineering. This includes sensing/response, motility, and communication between cells.

The focus on membranes as functional design elements in bottom-up synthetic biology is characteristic of our group.

With your colleagues Greta Zubaite, James Hindley, and Oscar Ces, you recently published a paper in ACS Nano. Can you tell us what you were able to achieve?

Biological cells are highly compartmentalized and the way the compartments are arranged is strongly related to the function of the cells. Over the years, many people have designed synthetic cells[1] with stationary compartments within them. But in nature, compartments are very dynamic. For example, they can appear and disappear, change location, and get released into the external cell environment.

So we tried to fill this gap and engineer a dynamic compartmentalization. We designed synthetic cells[1] where the compartments can switch from a highly organized to a highly disorganized state. In the organized state, the compartments sit on the surface of the membrane. They go to a highly disorganized state when they sense a change in the environment such as a chemical or mechanical signal. Depending on how we engineered them, they are either released into the surrounding environment or into the cell. No protein is involved to engineer this fairly complex set of responses, everything is done by engineering new types of bio-membranes.

What are the possible applications?

A learning-by-building approach can be very powerful. In terms of the big picture, this project and synthetic cell research in general can help us learn more about biology, and help us understand why almost all biological cells have compartments.

For concrete applications, the obvious one is for therapeutic delivery. Imagine a synthetic cell mothership[1] carrying small drug-loaded capsules on its surface and releasing the payload near a tumor in response to intrinsic or extrinsic cues. This is something we are currently exploring.

We also seek to have this switch from a highly organized to a highly disorganized compartment state linked to the regulation of cell function. This will allow us to activate different functions of the cell in response to external signals.

Image credit: Greta Zubaite

What was your favorite part of working on the project?

This project will always hold a special place in my heart because Greta Zubaite, who did almost all of the work, was my first PhD student. It was the first time I supervised a PhD student from start to finish. I trained her to be a scientist and saw her grow along with the project, which made me super proud. It was a great learning experience for me.

The European Synthetic Cell initiative aims to bridge the gap between research and technology to deliver smart, green innovations based on synthetic cell research. What are the key requirements for you to achieve this?

To translate this into applications, we need to address a number of challenges. As a community, we need to develop technology that would allow us to scale up the manufacturing process. We also need to build synthetic cells[1] that are stable for a sufficiently long time. Right now they are stable for experimentation, but for real-world applications, they need to be stable and active for longer, withstand cold storage and transportation. Finally, we need to find a robust way to build cells that behave as expected. There can be no uncertainty or irreproducibility.

I think the next phase for the community is to have research programs that fill this gap.

If you could be anyone else for a day, who would you be and why?

I would like to be someone doing something different so I could learn from this person. Synthetic cell research is really blue sky. We try to make life in a lab. The timescales are long and sometimes it’s hard to imagine the immediate real-world benefits. Some people have faced the same challenge, but they have been able to motivate their teams, get funding, and create public excitement. Teams working in space exploration are a  classic example. I want to learn from them, to learn how they did it. Our synthetic cell community is facing similar challenges so maybe we can do the same.

Which TED talk or podcast do you watch over and over?

I know it is cliché, but I am slightly obsessed with great entrepreneurs like Jeff Bezos and Elon Musk. I like hearing what they think successful innovation is, what good management and leadership is.  I don’t think they have ever given a TED talk, but if they did, that is what I would listen to.

What can’t you live without?

My children, but the superficial answer is coffee. Without coffee, I struggle to function physically and mentally.

[1] In this interview, the synthetic cells mentioned by Dr. Elani refer to artificial structures that are engineered to mimic some key aspects of biological cells, including cellular architectures, processes, or behaviors.