News

April Faculty Spotlight - Nicolas Fawzi

April 10, 2019
Ramisa Fariha
interview

As a kid, did you have an inclination of what you wanted to be when you grow up?

Absolutely! I thought I wanted to do science, and I told people that I wanted to be an astrophysicist before I knew what it meant! I always liked physics, and I wanted to do physics as an undergraduate. Also, my parents encouraged me to do something practical, like engineering. In the end, I am still doing physics- I go to American Physical Society and Biophysical Society conferences, and am essentially doing biophysics. I am doing the kind of physics that I liked- mechanics. I was never into the stuff that’s too complicated -haha. My father is a PhD pharmaceutical chemist. He spent his career in many different pharma companies. Both my parents emphasized education, and my father always told me I should be a chemist, but I told him I don’t really like chemistry. I still do a bunch of it, and I could have ended up in the chemistry department if I wanted to. I learned that he was right! Even though I don’t have a chemistry degree, I still apply a lot of it.

Do you have an inspiration that drives you?

My family was a big support to me, and cultivated this interest in me. I am still learning from my father- scientifically and professionally. I talk to him about what I am doing and the interface of it in the pharmaceutical industry. Also, I am a structural biologist, and what a lot of biologists do, is get inspired by looking around at the nature so I’ll call nature an extrinsic motivation. If I rephrase the question to what inspires me, I really like this job and the opportunity to do self-directed research. That’s neat. The other side is that, it’s about training and mentoring students, and there’s something very special about that opportunity that I really appreciate. If you want to make an impact on human health, it might be easier to do that in an industrial setting. But I’ve seen students- some are already phenomenal before you’ve met them, and with some students, you are able to help and show them what they have inside, and bring out their potential by working with them in a place like Brown- that’s been an inspiring part of the job.

How would you describe yourself as a mentor?

I won’t describe myself as tough, but I have high standards -haha. I have had some interesting interactions with some students recently, and it has made me be more intentional about the project planning that I do. Now we are trying to get everyone on the same page, and the students can contribute to everything from planning and designing, to working with collaborators and the end goal of the project. Now, they are not only part of the execution, but are also involved in the planning of a project. That’s such an important thing, in order to get something done.

Of everything that you have accomplished so far, what is the work/publication that you’re most proud of?

I have one thing that stands out in all of my different stages, but if I were to pick one, I think as a postdoc, we were trying to see the structural details of these protein aggregates that no one had ever seen before, and even though I didn’t have years and years of technical experience, I was able to come up with a new experiment to visualize these previously invisible states. What has been satisfying is that the work has been expanded upon dramatically by others in the field, including some of the leaders in the field. So I feel like my work inspired them, and it’s pretty cool that we were the ones who thought of it first, and demonstrated it. And it spawned like a whole series, and dozens of papers have utilized this. It was a team effort, but I had the idea.

Here at Brown, we were able to make a liquid form of this protein that associates and assembles into the membraneless organelles in cells that I mentioned earlier. And we made a mimic of it in a test tube, and we were the first ones to publish the structural details of the in vitro mimics of these assemblies. It was challenging, and it hasn’t been achieved by many people, and I was only two years into my career here. So it was satisfying that we were able to do something new so early on in my career.

What’s your favorite course to teach at Brown?

Answer: My classroom teaching is focused uniquely on this class that I’ve designed called Biomolecular Interactions: Health, Disease and Drug Design (BIOL 1300 and 2300). It’s a physical approach to biology- how do organisms and all their biological processes work, what goes wrong in disease, how do drugs work, and it’s really all by molecules interacting with other molecules. So it’s a class where we focus on those questions, and ask what are the interactions that drive physical functions, how do you determine those interactions, and discover interactions between one molecule and another molecule, quantitate those interactions, and design interactions for new therapies. That’s my favorite course to teach. We read a lot of papers, and the undergraduate version of this class has a writing designation, where students have to write these short summaries in Cell Press style, and write a research proposal at the end of the semester. It’s something I thought I could contribute to the student experience- so not just the technical stuff, but also the writing aspect and communicating science to other scientists. I felt I could make a contribution towards helping students develop an important skill.

In science, experiments don’t always work. How do you manage with the stress of failure? How do you address failure and keep moving forward?

Answer: I guess, my approach has been (and this has been encouraged by my PhD and postdoc advisors) that, if you start working in an area where people are looking for answers and you bring in new tools and expertise to it, then almost whatever you find will be important. And from training in biology, if you set up an experiment and it doesn’t work, it will still have outcomes that advances knowledge, and you will find something that no one had known before. That’s something very attractive about science. As a postdoc, we were trying this experiment, and there was some artifacts that kept happening and the experiments didn’t work. But that’s how we discovered that we needed to utilize a different technique. You have to be ready to turn the lemon into lemonade, and take advantage of the new opportunities that present themselves as failures. If everything goes according to plan, then you haven’t learned anything. As a professor, I encourage my students to do the hard experiments that no one’s done before, and that’s how they have the potential for some really cool findings. We have had a lot of successes recently, and I look back at things positively- even at things that didn’t work. If you design experiments that reveal interesting information, regardless of the outcome, even technically failing experiments contribute a lot to the learning process. In terms of other failures, I have had a lot of grants get rejected, and I shrug it off, and tell myself, “Well, they don’t know what they are talking about!” haha. I even tell this to students, who are looking into certain fellowships, that they may be the perfect person according to the job description, but there are so many factors behind the scenes that influence a decision.

What are the three qualities that are crucial for being a successful researcher?

Answer: You have to take some risks. Trying to do something new is risky. And you have to be ready to see things from an alternative viewpoint when something is not working. And sometimes you need to step away from a problem in order to think clearly. I go biking, and distance myself, to give my brain some time to do its thing. Give yourself space to come up with new insights.

 

Dr. Fawzi is a new trainer in the BME graduate program so we also asked him some questions to introduce his research to the Brown BME community:

What has your journey been like in the Biomedical Engineering field? How did it start?

I decided to go to graduate school because I thought I wanted to be a professor. I was an undergraduate student of Bioengineering and Business in Engineering in University of Pennsylvania. I thought I was going to do business development for biotech companies, but felt this calling to science and so I decided to look at PhD programs and went to University of California, Berkeley, which had a joint graduate program with UC San Francisco for Bioengineering. They had a broad definition for Bioengineering and you could do research rotations with different faculties. After doing a few rotations, I learned about protein structures and interactions when I met a professor there, and decided I wanted to continue on that path. And even though I had done engineering, I ended up becoming a biophysical scientist.

What was your research in graduate school? And how did it lead to what you are currently working on?

As a graduate student, I did molecular simulation, trying to understand how do molecules move, bind and fold proteins. It is hard to visualize because they are so small and you can’t see them under the microscope with that resolution. But with molecular simulation, you can get videos of what’s happening in a simulated fashion, and you can ask how do changes in the proteins lead to forming these protein aggregates. But it’s hard to validate these, and know what we are seeing in the simulation is what’s really happening in a test tube or a human being, to understand how a mutation causes a disease. As a postdoc, I started doing experiments to examine the same questions of protein assembly, aggregation and interaction using NMR spectroscopy. My work was to understand how does the protein amyloid beta self assemble into these toxic aggregates, and the structure of those is still not completely clear. What I wanted to do was examine the structural details of these assemblies, and so we had to develop new techniques in order to do it.

Now, as a faculty member, my interest is to look at proteins that hadn’t been looked at before, that are involved with neurodegenerative diseases that are also associated with protein aggregation. There’s a family of diseases- ALS/Lou Gehrig's disease and frontotemporal dementia- and these conditions are also associated with neuronal protein aggregates. We want to understand how do these mutations that are associated with familial forms of these diseases, actually cause these diseases, and what do the proteins look like along their aggregation pathway. That’s what I am doing today, and my research area has exploded an interest in cell biology. There are compartments in the cell- like nucleus, mitochondria- and people think of these compartments as bounded by membranes. But what’s being appreciated is that there are these compartments that have no membranes. The best known one is the nucleolus- a compartment inside the nucleus that’s been seen by microscopy for hundreds of years, but it’s not clear what it really is. Turns out, it is not bound by a lipid membrane, and it’s actually a liquid that’s separated from the rest of the nucleoplasm by liquid-liquid phase separation. So essentially it’s the same thing that separates oil from water in salad dressing. That’s why the nucleolus is in a distinct phase, and actually there are at least two different liquids in the nucleolus in some organisms. That’s only one example. There are these other smaller compartments that appear to be liquid-like assemblies. What ended up happening is that, the proteins I was interested in, a number of them localized to these compartments, and some of these compartments are linked to neurodegenerative diseases. So we are trying to understand not only how these proteins form solid aggregates in diseases, but how do they form these functional liquid-like assemblies, what stabilizes these normal physiological compartments of membrane-less organelles and how do they go wrong in diseases. That’s the area my lab is currently looking at.

So your interest in investigating ALS and related diseases was sparked by your interest in protein biology?

Yes, exactly! So we are doing protein chemistry, essentially. And, I was interested in the process of protein aggregation which is a feature of these neurodegenerative diseases such as Alzheimer’s, ALS, Huntington’s Disease, Parkinson’s Disease, but the mechanistic process of what do aggregated states really look like is only just starting to be illuminated, and that’s the area of structural biology, which includes atomic level of structural details. So we’re trying to see what are these states, because we don’t really know what the problem is.

How will your research translate to actual medical applications?

All these neurodegenerative diseases have these protein aggregates, but no one really knows are these aggregates causative, or, are they toxic, and one problem towards answering these questions is we don’t even know what are these things, and what do they look like. In some ways, it’s different from diseases like cancer, where we know what the problem is. But with these neurodegenerative diseases, we don’t even know what the problem really is. We know there are these hallmarks, we know some of the genetic pathways from familial diseases, but we don’t really know the underlying molecular problems that lead to these diseases. We are trying to look at it at the source, and the idea is that if we know what these structures are, we will be able to develop new therapies. And the cells are always modifying these proteins with post-translational modifications, and these modifications are just as big of a chemical change as the mutations that cause the familial forms of the diseases. If we can understand where should we get these proteins modified so they don’t do these bad things, the cell might already have a machinery to do so if we told them to do so.

You mentioned how you went from business and engineering to a molecular biology route. What was the exploration and transition like?

To be quite honest I felt like I didn’t know what I was going to do. I was an undergraduate going into my senior year, and I thought I was going to work for a consultant company. But I did this summer urban service kind of project. It was through a Christian organization that had placed students in different non-profits for the summer. I volunteered, where I was helping people start small businesses in Philadelphia, and I realized that I was missing science. At the same time, through this program, I was asking God about what’s my calling. And I realized that my calling is to be a scientist, and thought that the way to practice this is to be in an academic path and be a professor. I was interested in business but I wasn’t really passionate about it. So I asked myself what was I most passionate about, and the answer was science and engineering, that eventually led to choosing a broad PhD program.

I wanted my field to be more applied science and Tissue Engineering seemed very attractive to me. But after going through different rotations, I ended up choosing molecular biology. I was interested in teaching as well, and I thought being a professor as a career would be exciting and was a good fit for me. I looked at what was out there to get to where I am today. I was just so passionate about it, I didn’t feel like I was missing out on the industry-related opportunities. Also, the stress and anxiety of getting a job was very different seventeen years ago, when I graduated. The business background has been helpful to me, because the undergraduate business education was really broad. To date, I’ve been applying what I’ve learned- I have budget spreadsheets, I have a team that I have to manage, in some ways I have to sell myself and my work, so it’s a lot of marketing, accounting and management. These skills are important outside a traditional business job, even in a STEM-field.

Was it easy to get into a program of your choice, given you didn’t have the necessary research experience? What would you say to students who might make similar choices?

I didn’t have a lot of research background, and didn’t get into Harvard, MIT or Duke, where they had research-intensive Bioengineering programs. I was transitioning from a different program, and it gave me a different perspective. It’s getting better now that some of these traditional disciplinary boundaries are coming down, but if you want to do something quantitative, it’s helps to have a quantitative background. When I decided to go to graduate school, on my senior year, I went back to take all those quantitative courses to have my bachelor of science in engineering degree. I wanted to show that I have quantitative skills, and got a degree that I thought would help me. It’s a balance- where you can demonstrate that you can acquire the skills you need to do something you want, and you have the passion to do it.  

What led you to applying to be a professor here at Brown?

When I was a graduate student, I thought I wanted to be a professor at a teaching institution, like a liberal arts college. Then, at the end of my PhD work, I decided to do a postdoc because I was curious about the protein NMR spectroscopy that I am doing now. I really enjoyed research, and I thought being a professor at a research university would be the appropriate next step and something that I’d be excited about. I searched nationally for positions, and Brown had acquired the instrumentation that would have been a good match for me. Brown was looking for someone in a narrow field, and I happened to be in this narrow field. And I really liked Brown’s balance of research and teaching. They were looking for someone to make use of this great resource they had acquired, and I wanted to be at a place that had the infrastructure to support the specific thing I wanted to do.

Finally, what are you aspiring to? What will be your moment of highest achievement?

I don’t know if I can answer that question haha. I try to live in such a way, that if I were to die now, I’d be okay with it. There are a number of things that can take up your time, and the most challenging thing is to remember that I am not just a scientist, but I am a husband, a father and a son, and being present where I am.