First person – Lior Peer Free

Lior Peer

How would you explain the main findings of your paper in lay terms?

Our bodies are composed of cells, the smallest units of life. Each cell comprises specialized compartments called organelles, which create distinct biological and chemical environments for specific cellular processes. One such organelle is the peroxisome, which is crucial for breaking down fats to produce chemical energy and clearing harmful compounds. In humans, the loss or even partial dysfunction of peroxisomes leads to severe genetic diseases and contributes to many pathologies, including cancer, neurodegeneration and aging. Therefore, it is crucial to extend our understanding of the vast and versatile biological processes occurring in peroxisomes and the functions of the proteins that reside there. Therefore, we need to know how these proteins find their way to the peroxisome, or in other words, how proteins are targeted to the peroxisome. Our paper focuses on a peroxisomal protein called Eci1, which is a part of the machinery that degrades fats inside peroxisomes. Certain types of fats cannot be broken down without Eci1. For many years, it was unclear how Eci1 is targeted to the peroxisome. Although one specific part of the protein was known to carry targeting information, Eci1 was still able to reach the peroxisome even without it. We found that Eci1 has additional targeting information, embedded within a previously uncharacterized region of the protein. This region enables Eci1 to interact with Pex5, the major protein ‘shuttle’ that transports cargo to the peroxisome. This finding sheds light on an additional mechanism by which peroxisomal proteins find their way into their target organelles, widening the existing dogma.

Were there any specific challenges associated with this project? If so, how did you overcome them?

To examine our hypothesis of an additional, non-canonical binding interface between Pex5 and Eci, we needed a full-length structure of Pex5, which had not been achieved before and was highly challenging. However, we found that co-expressing full length Eci1 and Pex5 proteins stabilized Pex5, allowing us to identify the structure of parts of Pex5 never observed before. Those parts include the amino acids interacting with Eci1 in the newly uncovered interface, which we named the Eci1-binding interface (EBI).

When doing the research, did you have a particular result or ‘eureka’ moment that has stuck with you?

Oh Yes! I remember the first time I saw our cryo-EM structure of the Pex5–Eci1 complex. I was in awe of how beautiful and informative it was, revealing many details about the intricate interaction between Pex5 and Eci1. Specifically, I remember when I first laid eyes on the newly discovered interaction interface, which included previous unseen amino acids in Pex5. In that instance, our microscope observations were affirmed, and we saw an additional binding interface between Eci1 with Pex5, distinct from the peroxisomal targeting sequence type 1 (PTS1). It made perfect sense, and all the pieces fitted together perfectly.

Why did you choose Journal of Cell Science for your paper?

We aimed to publish in a journal that supports early-stage scientists like myself, while providing a platform to share our scientific discoveries with a broad spectrum of scientists interested in cell biology. Since our article comprises both structural biology and cell biology research, we wanted a community journal where editors are scientists and can appreciate the interdisciplinary nature of our work.

What motivated you to pursue a career in science, and what have been the most interesting moments on the path that led you to where you are now?

I have always been fascinated by how things work around me, especially in nature and life. Many children have a stage early in life when they constantly ask ‘why’, and I believe that stage will never end for me. My curiosity about what enables the processes around us, whether it's a flower blooming in spring or how our food turns into chemical energy, has always intrigued me. This curiosity led me to start my undergrad studies in plant science. I vividly remember a month into the first semester, when we first learned about DNA. That was the moment I realized I was in the right place. Two years later, during my last year of undergrad studies, I performed my own research project working with plant cell tissue in cotton. This was my first experience with transforming genetic material into a living organism and performing the experiments made possible by that transformation. From then on, I realized that scientific research was my passion in life, and I intend to continue with this passion.

Who are your role models in science? Why?

My role models are Prof. Maya Schuldiner, my advisor, and Dr Einat Zalckvar, who was my M.Sc. mentor. They are not only extraordinary scientists but also amazing mentors who taught me almost everything I know about how to do science, from the conception of a hypothesis to critical thinking and reading, and even maintaining a healthy work–life balance. I am truly grateful for their mentorship, and I wouldn't be where I am today without their support.

What's next for you?

Currently, I am halfway through my PhD and remain deeply fascinated by peroxisomes. I am working on a new project regarding uncovering new peroxisomal proteins and their biological functions. After completing my PhD, I plan to continue to a post-doctoral position and eventually lead my own research group.

Tell us something interesting about yourself that wouldn't be on your CV

I really love learning new languages. Currently, I have my eyes set on Romanian, which I recently started learning, mainly to speak to my mother in her childhood language.