February 2021 Paper of the Month

06 April 2021

Congratulations to the February Paper of the Month winners: Doctors Nir Salinas and Einav Tayeb-Fligelman from Prof. Meytal Landau’s lab, for having their paper accepted for publication in PNAS. We used this opportunity to ask them about their research, the stories behind it, and a little bit about themselves

Hi guys. Can you tell us few words about yourselves?

“Einav Tayeb-Fligelman, postdoctoral fellow at UCLA and mother of three. I got my B.Sc. from the Faculty of Chemistry at the Technion, in the Molecular Biochemistry program; my M.Sc. I also got from the Faculty of Chemistry, in Prof. Timor Baasov’s lab; and my Ph.D. I completed in Prof. Meytal Landau’s lab at the Faculty of Biology.”

“Nir Salinas, postdoctoral fellow at The University of California, San Francisco. My journey at the Faculty began in 2012, when I started my B.Sc. studies in the Molecular Biochemistry program. In my final year of study, I joined Prof. Ariel Kaplan’s lab as a research assistant. That was my first research experience. It was so meaningful that I decided to turn it into a career. Right after I finished my B.Sc., I started my complementary studies for an M.Sc. at the Faculty of Biology, and then proceeded to the direct Ph.D. track under the supervision of Prof. Meytal Landau in the functional amyloid fibril lab. I parted with the Faculty in September 2020 to move to the US for my postdoc, in which I study the structure and function of ion channels in neurons.”

Briefly, what does the Landau lab do?

The Landau lab studies the structure-function relationships in functional fibrils that originate in different organisms or their derivatives. It concentrates in amyloid-like substances and other functional fibrils which have an interesting [atomic] structure and function, and better understanding of which may help scientific progress in the fields of drug development or nanomaterial engineering. Amyloids are protein fibrils that have a very specific and defined structure. In the past, they were associated mainly with degenerative diseases of the human brain, such Alzheimer’s and Parkinson’s, but now we know of more and more such fibrils that can serve the organism that produces them, be it human, other animals, or microorganisms such as bacteria or fungi. Examples of such fibrils’ functions include antibacterial activity or toxicity to other types of cells, adhesion to various surfaces and changing their properties, forming a protective biofilm in bacteria, and much more. As we were studying functional amyloids, we discovered some new functional fibrils which are not amyloid (have different structures), expanding our understanding of the structure-function relationships in functional fibrils as a whole. Understanding the structure-function relationships of such fibrils may allow more efficient development of drugs against fibrils produced by pathogenic microorganisms, and help us find ways to imitate nature and create similar fibrils which would help people, such as the fibril described in our current research.

Tell us about your current paper/study. What was the purpose of your research, and what have you found?

In the course of the research described in our paper, we studied an antibacterial peptide secreted on the surface of the skin of the Uperoleia mjobergii (Australian toadlet). This peptide forms inactive amyloid-like fibrils on the toadlet’s skin, probably as an efficient way of storing the peptide. But in the presence of bacteria, the peptide in the fibril changes its structure – while maintaining its fibril form – and becomes active and toxic to bacteria. We assume that this mechanism of action by the peptide in the functional fibril is a quick and efficient way for the toadlet to defend itself from harmful bacteria as soon as they merely touch its skin.

Could you explain the importance of this discovery?

Understanding the function of that fibril and the unique structure of the peptide that forms it and activates in response to bacterial threats can help us develop similar fibrils that would provide topical treatment of or protection against bacterial contaminations, whether in the form of an ointment that one would apply on the skin, or as coating for sensitive medical equipment that may get contaminated and spread infections from patient to patient. It can also help us plan potential modifications of the fibril, to provide protection against specific types of bacteria or against other microorganisms, such as fungi etc.

Please tell us some more about the process of your work, and how you came up with the idea…

The research took about 3 years. We started by looking for some interesting functional amyloid fibrils, aware of the growing understanding of the connection between such fibrils and antibacterial peptides. As we were reviewing the literature, we found some clues indicating that the peptide uperin (subject of our paper) may be forming functional amyloid fibrils, but a lot of information was missing, and there was no structural information at all. When we started studying that peptide, we became particularly intrigued when we realized the fibrils it forms have a completely new and unique structure; that was a discovery made by our lab and published in Science Journal in 2017. We became even more curious when we discovered that the structure of the fibril and the activity of the peptide change depending on the presence or absence of bacteria. If at the beginning of the study we wanted to prove uperin’s ability to form amyloid fibrils and to discover their atomic structure, as we were working on it, we realized we were dealing with something much bigger… like a natural Transformer, which transforms and gets new abilities when faced with a threat.

Any interesting/funny stories from this research?

Like every project we do together, this one was lots of fun. Much of the fun takes place during our trips to particle accelerators in Europe, where we spend 24 hours collecting the atomic diffractions of protein crystals, and then go to the local bar or take a walk around the town. Those trips involve a lot of hard work and fatigue, but also a lot of fun, laughs, late-night snacking, and just good team time. In the Landau lab we became true friends, or as Einav likes to call it, “biological siblings from different parents”. Right now, we’re both doing our postdocs in the US, and we remain in close touch.

An interesting story from this specific research is about how we managed to determine the structure of the uperin functional fibril. Its structure was very difficult to decipher, but while we were working on it, Einav went to a convention in the US, where she met with some of the best minds in structural biology, the people who are developing the very software and techniques we use to determine atomic structures. Einav spent every spare moment she had and the end of every day with those scientists, trying to study the data we gathered from the particle accelerator, to figure out and solve the problems, and eventually together they managed to decipher the fibril structure, help the technique developers understand the unique challenges of deciphering structures of this kind, and make some important work connections.

How important would you say creativity is in science?

Creativity is key in science. Virtually anyone can be taught to make measurements and use equipment, but not everyone can think science, see with their imagination things that cannot be seen with the eyes, or think out of the box. Creativity also means understanding how you can use certain methodologies in your research, even if nobody had used them before in research that way. Creativity allows us to develop new methodologies, and to make assumptions and gain insights that are not immediately obvious. Even if many of those creative assumptions prove to be wrong, you can discover so many new things while you are studying them, and then creativity means realizing and understanding what you weren’t expecting to discover, and the meaning of those discoveries. Other important elements of science are courage – courage to try new things and to keep failing until you succeed, not being afraid of failure or of trying a new methodology, but most of all – being open to every possibility, because the most meaningful things are often found where you’re not looking for them.

What do you do when you’re not doing science?

Einav: “I raise my kids, sing, dance, go to the movies (when the theatres are open) or just watch TV, but… It doesn’t happen very often (except for the “raising my kids” part).”

Nir: “Even though a career in science is very demanding and doesn’t leave much spare time, when I do have some, I like to take walks with my husband and our dog, cook and bake to make sure we have enough snacks, and if I still have some time left – exercise a little.”

What is the one thing no one knows about you?

Einav: “I was born and raised in Ramla. Both my parents were born in Israel, and my grandparents came from Morocco, Libya, Tunisia, and Jerusalem. When I was growing up, I didn’t even know there was such thing as the Technion, until a representative came to our high school, which was then called Ramla-Lod High, and told us about the Technion and what it does. It was then that I set myself a goal: I’m going to go to the Technion! And so I did, for all 3 degrees! I was the first in my family to go to university, and even though none of them truly understands my world, their love, support, and belief in me was all I needed to know that I can succeed in that new and unfamiliar place, if I only work hard and have faith. Over the years, and when I was volunteering in Perach, I realized the extent to which children from similar backgrounds feel they don’t have the tools and the ability to succeed, and that makes them lower their ambitions. This understanding has never left me, and it made me want to make a difference! One of my choices was to keep my maiden name – Tayeb – alongside my married name Fligelman, to maintain my identity and declare that it wasn’t in spite of my background, but because of my background – which I’m proud of – that I got where I am today. Currently, as a postdoctoral fellow at UCLA, I am the manager and co-founder of a group of women in science. The purpose of our group is to promote gender equality in every level of science, and to empower women in science and elsewhere. I’m now working on expanding the group’s activity to include other minorities (of either sex) as well, and waiting for the opportunity to do something similar in Israel. The more I get involved in this, the stronger my desire to help make a difference. Like that representative of the Technion who came to my school to tell us we could do it too, and made all the difference for me. I believe the change starts with us – women, minorities, disadvantaged groups, people who should and can be taught to believe in themselves and in their abilities. Alongside my research work, I intend to continue acting for equality in science constantly – wherever I am.”

Nir: “If I weren’t a scientist, I’d be a shrink.”

What do you want to be when you grow up?

Einav: “An independent researcher, mentor, and opinion leader. I want to go as far as I can in whatever I choose to do, taking along good people who need some guidance.”

Nir: “I’m already grown up, and I still don’t know. Although at the postdoc stage I’m supposed to focus more on my career, I’m really looking forward to the next phase in my personal life, which is starting a family. I suppose the pace won’t ever slow down, so why wait?”

And what about your career plans?

Einav: “My plan is to start – hopefully in the near future – my own lab, which would also focus on structure-function relationships in proteins, and to keep making groundbreaking discoveries through innovation and integration of different methodologies. My goal is to become No. 1 is my field while raising generations of great and happy scientists, like Prof. Landau and like my current postdoc supervisor.”

Nir: “I want to keep doing research in order to enhance our knowledge and understanding of biochemical processes that take place in the human body on the molecular level, and to understand how we can improve and advance medical science and the treatment of diseases.”

Finally, any tips for new students?

Einav: “Keep your head high and keep moving forward! There will be many difficult moments… Sometimes you’ll want to just give it all up but remember the greatest opportunity for growth lies in the greatest difficulties.”

Nir: “Never abandon your natural curiosity, which drew you into research to begin with; and remember – a day in which you didn’t learn anything is a day wasted.”

לינק לאתר מעבדת לנדאו: https://mlandau.net.technion.ac.il/

קישור למאמר: https://www.pnas.org/content/118/3/e2014442118

 

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