Hughes Mentor:  Gerald Feigensen

Department: Molecular Biology and Genetics

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A Day in the Life of an Undergraduate in the Feigenson Lab

During my freshman and sophomore years, I had heard about the many different research opportunities that are offered at Cornell. I too wanted to get involved with research. I was interested in working in a Biology lab, but I was not sure what type of Biology lab. I read various research descriptions on the Biology research website and found many labs that seemed very interesting. Out of all of them, the Feigenson lab intrigued me the most because it was biologically relevant, but much of the research was chemistry-related, which is my major at Cornell. I looked on his website and read a few of his recent publications. I then emailed Professor Feigenson and asked to meet with him to discuss his research. After talking with him and attending a group meeting, I was very excited to work in the lab doing biomembrane research.

The Feigenson group is interested in the chemical properties of biomembranes, particularly how lipid-lipid interactions influence membrane heterogeneity, or phase separation. In my lab, we map out phase diagrams of different lipid mixtures. The phase behavior of the membrane lipids can have many biological applications. One of these is regarding virus entry and exit. It is possible that viruses like the HIV virus can only bind to specific membrane phases. Understanding the phase behavior of membrane lipids can allow us to understand how certain viruses attach to biomembranes. Another application of studying phase behavior is concerning hormone signaling. A hormone signal can bind to a region on the membrane and induce a phase change on the surrounding lipids. This can then facilitate the movement of proteins into or out of the cell. Then, the signaling pathway can be initiated.

As a member of this lab, I work on tracking the movement of a previously solved three-lipid diagram (consisting of Cholesterol, DSPC (distearoylphosphatidylcholine), and DOPC (dioleylphosphatidylcholine)) with the addition of a fourth lipid, SOPC (stearyl-oleyl-phosphatidylcholine). My project includes making Giant Unilamellar Vesicles (GUVs), or artificial bilayers. These bilayers can serve as a reasonable model for real biological membranes. Making these GUVs is a one day process including creating a mixture of the lipids, spreading a “film” on a slide, vacuum drying the slides, adding a sucrose buffer, and then running a current through the slides. The next day, I harvest the vesicles and look at them under a microscope. I use a fluoresce microscope to see partitioning of two fluorescent dyes and decide whether the vesicles have coexisting phases or only have one phase. My data includes many colorful pictures of the vesicles that I create. I also have opportunity to compare my data with that of graduate students in my lab who are conducting similar lipid mixtures but with different experimental techniques.

On other days in my lab, I perform other important lab procedures such as testing the purity of my lipids by doing a TLC or calculating the concentration of my lipid solution by doing a phosphate assay. During the first few weeks of this summer, I also did many lab-related tasks such as defrosting the freezer and washing vials. All of my lab projects are done in a very friendly and sociable environment. Working in the Feigenson lab is both challenging and fun. I wouldn’t spend my undergraduate years in any other lab!

A Day in the Life of an Undergraduate in the Feigenson Lab

• What did it take to get into this lab? How did you find this opportunity?

I ended up doing research in Professor Feigenson’s lab, not because his research subject is of particular interest for me at the beginning. Instead, it was because he had a strong bond to his students and I felt like I could learn a lot for him. Also, it was luck too.

I met Professor Feigenson in the biochemistry class in my first semester at Cornell. Professor Feigenson is one of those few professors who present in such a way that you don’t have a chance to be confused. I started to talk to him often after classes or in his office hours. First, we discussed the biochemistry subject issues, and then we moved further to talk more about his path of becoming a professor at Cornell, and my goal of being a researcher.

Once I mentioned to Professor Feigenson that I wanted to join a lab on campus. He, unfortunately, couldn’t take me at that moment. Still, he generously provided me a list of the most possible professors who could take me. Failing a number of trials with the professors on the list, I came back to Professor Feigenson and asked for help again. To my surprise, he invited me to join his lab. It turned out that he made an effort to organize his group so that he could take me and another undergraduate student. I happily accepted his offer and I started doing research in his lab this semester.

If one wants to join the Feigenson lab, the best way to talk to him sincerely and express a great interest. If it is possible, Professor Feigenson will make definitely room for you.


• Do you need any information that you learned in specific courses?

Of course, some information I learned in general biology course are useful in laboratory, in terms of experiment design, data interpretation, etc. However, in this lab, the research topic is not quite common that I can not find any example of applying specific information I learn in specific course to the research that I am doing. In other words, you do not need to have taken a specific course in order to join this lab. The skills required in this laboratory are very particular, and you have to learn it after you join the lab.


• What is your day like in the lab?

In a typical day, the actual time I spent on doing experiment is not too much; what actually take time in many experiments is waiting time. Over these months, I have developed my own way to utilize the waiting time.

Typically, I start something immediately after I arrive at the lab in the morning, then I may sit down to do some calculation for the next step. After this, I continue to do the experiment. During the next gap, I would probably spent the time collect and look at the samples that have sat over the night before and ready to be analyzed. Then I may continue to do the experiment, and use the next gap to organize the data I obtain. Usually before I leave for the day, I set aside something that needs to sit overnight and I would deal with them the next day.

In a word, waiting time management is very important in our lab. These gaps can also be spent on lunch, group meetings, seminars, and maybe a little bit of one’s own things. In this way, a day would be packed and fulfilling.


• What organism or molecule do you work with? Is there anything special that you have to do to work with this?

We are not working directly with any organism, not even cells. Instead, our focus is lipids, including glycerolipids, such as phosphytidylcholine (PC), sphingolipids, sterols, such as cholesterol, etc. There is probably only one thing we do to these lipids—to prepare GUVs (see the following question for more detail) and characterize them. That’s what our research is all about.


• What techniques are you using?

Phosphate assay is the entrance technique every new member of the lab needs to learn. It is actually just a moderate quantitative assay used to accurately measure the concentration of lipid stock. However, accurate concentrations of the lipid stocks are so important to our research that without this technique, no further experiment can be done!

GUV preparation is the central technique I am using. It includes a series of carefully designed procedures, including “clicking” lipids mixture, spreading the lipids, vacuum evaporate the solvent, electroswelling, and sample collecting. It takes me months to master this technique.

Fluorescent microscopy is another main technique I am using. Similarly, it takes time to master the “temper” of the fluorescent microscope.


• What have you learned about yourself and research from doing this project?

The biggest finding from doing this project, besides the results of the experiment, is something about the nature of scientific research: an active researcher learns something new everyday.

At the stage of planning my project, I thought this was going to be a boring project because of many repetitive steps. As I carried out of the experiments, I realized this project, as well as scientific projects in general have no way to be boring at all. The reason is that even the procedures are the same, the results can be different, sometimes even the exact opposite of each other. Also, during the process of the experiment, plenty of novel observation would appear to surprise you. Then different people in the lab often have a unique way to interpret these ambiguous or unexpected results, and we discuss and learn from each other. In a word, knowledge can be obtained at any moment in the lab.


• What kind of students should be interested in your lab?

Because the topic of our lab is quite different from the typical biochemistry lab, students who are sort of tired of the common topics would be interested in the Feigenson lab. Because our lab doesn’t deal directly with organisms or real-life applications, students who prefer theoretical sciences to applied sciences would love to work in this lab. Last, because of the kind, comfortable environment Professor Feigenson and other lab members create, 90% of the biology majors, I believe, would love to work in this lab, regardless of their concentrations.


• If you were in the lab during the school year, what is different about research during the summer and the academic year? Any advice for balancing research and academics?

One obvious difference between research in academic year and summer is time management. In general, there are lots of benefits doing research in a summer program like the Hughes Program rather than in school year.

The Hughes Scholars Program provides me with a unique opportunity to do research that I cannot find during school year. When classes are in session, it is simply impossible to devote myself completely into research. In the Hughes Program, I can work full-time, which will bring up my highest productivity. I can also do experiments that last for weeks, which is not possible during school year.

Outside the research itself, the Hughes Program also provides us with various activities to train us with the requirements to be successful researchers, such as meeting with other Hughes scholars and presentation. These intellectual exchanges are particularly important because nothing can be done without the full cooperation of a group of people in the modern world. Therefore, communication skill is essential for scientists of tomorrow.


• What do you do for fun while waiting for incubations to end?

For myself in this summer, honestly, I would take out the GRE prep book to study, because I will be taking the GRE test in the coming fall semester. That’s also true for many Hughes Scholars.

But for everyone else, things I suggest to do could be lunch, seminars, or simply hang out with people of the labs next door. It is always good to know your neighbors because you don’t know when you would need to borrow the spectrometer or a bottle of liquid nitrogen from them.

A Day in the Life of an Undergraduate in the Feigenson Lab

I have always been amazed by how biology and physics, two seemingly unrelated disciplines, can complement each other, especially in areas like Biophysics. My research experience with the Feigenson lab has exposed me to the immensely exciting field of Biophysics.

Prof. Feigenson taught me for BIOBM 331 in the fall semester of my sophomore year. He showed the class some of his Biophysics research on lipid phases during his lecture and simply fascinated me. I did very well for BIOBM 331 and Prof. Feigenson sent me an email to congratulate me for my excellent performance. It was then that I realized that he is the director of graduate studies in Biophysics. I told him about my interest to do graduate school in Biophysics and was looking for a research project relevant to my interest. We had a great chat and I realized that his research area coincides nicely with my interest. I requested to work in his lab during our meeting and I am really grateful that he offered me the opportunity.

The research focus of the Feigenson lab is on biomembrane phase behaviors. Biomembrane is a complex bilayer mixture of lipids and proteins. Depending on the interactions and arrangements of the components, biomembranes can have different appearances – membrane phase behaviors. If you are interested in the biophysical interactions underlying membrane behaviors and functions, the Feigenson lab will prove to be an exciting place to start your exploration.

We are particular interested in developing a model system for animal cell plasma membrane. In our current system, we use a mixture of lipid components (distearoyl-PC/dioleoyl-PC/cholesterol) to generate artificial membranes. Though this mixture serves as a chemically simple model, one inherent problem is that distearoyl-PC (DSPC) is not abundant in real biomembranes. My research project involves the improvement of the current membrane model system by gradually replacing DSPC by sphingomyelin, a lipid that forms one of the major components of animal cell plasma membrane. We would also like to investigate how the membrane phase behaviors would change when sphingomyelin is introduced to the current model system as the fourth lipid component. The significance of this project is to produce a good model for the behavior of real animal cell membranes and to enable much better understanding of biomembrane phase behaviors.

One of my main tasks is to create artificial membrane for developing the model system. To analyze the effect of sphingomyelins, I need to prepare giant unilamellar vesicles (GUVs) with varying concentrations of sphingomyelins. These vesicles are bound by a layer of lipid membrane and are filled with water. They are prepared by eletroswelling. As the name suggests, this procedure involves running electric current through a thin film of lipid mixture to generate the vesicles. By using fluorescent dyes that selectively partition into the various lipid phases on the vesicles, measurements can be taken to analyze how phase behaviors of the membrane changes as DSPC is replaced by natural sphingomyelins from porcine brain, milk and egg.

An Interview with Professor Gerald Feigenson

Scientific exploration runs through Professor Gerald Feigenson’s veins. While other children were still begging their parents for bikes and other assorted toys during the Chanukah season, he asked for only one thing, a chemistry set. At the age of eight, he could be found in his living room mixing potassium nitrate, sulfur, and charcoal to produce gunpowder. He pursued his passions well into college where he excelled as the top chemistry student in his class at Rensselaer Polytechnic Institute. He went on to earn a Ph.D. in Chemistry from the California Institute of Technology and published his first paper in the journal, Nature. After a seven-month postdoctoral study at Oxford University in 1973, he finally settled down at Cornell as a Professor and researcher of Biochemistry.

Professor Feigenson’s research revolves around the physical and chemical properties of membranes. Specifically, he seeks to understand the principles that govern the interactions between the three major bilayer components, lipids, proteins, and cholesterol. His hypothesis is that membranes are homologous to proteins in that their structure is determined by a basic structural property. For proteins, it is the amino acid sequence, but for membranes, it is still unknown.

This investigation may have far-reaching implications in the signaling field. For example, when hormones or allergens bind membrane receptors, this causes certain molecules to associate with each other forming clusters on the membrane itself. Thus far, no one has deciphered the mechanisms that underlie this event. Feigenson hopes that his work will eventually reveal the pivotal role that membrane structure plays in such cascade reactions.

Outside of the lab, Professor Feigenson does not spend all of his time writing and revising the lecture guide that all BioBM 331 students have come to know and love. Instead, he can be found along the Ithaca trails taking part in one of his favorite activities, hiking. He says that he does this in part because he likes to walk, and also because he likes to see the variety of ecosystems that exist at different altitudes. His words only prove that whether it is chemistry or biology, he remains a scientist at heart.

Hughes Interview with Jerry Feigenson

Jerry Feigenson grew up in the Washington, D.C. area. As a child, he showed a strong interest for the sciences especially chemistry. Dr. Feigenson received a B.S. in chemistry from Rensselaer Polytechnic Institute. At RPI, he spent four years conducting undergraduate research in a surface chemistry lab. During his senior year he became especially interested in biomembranes. Dr. Feigenson then moved to the west coast to conduct his doctoral study at the California Institute of Technology. As a PhD student he studied the structure and composition of biomembranes using NMR techniques. He left Caltech with a PhD in chemistry and a minor in French, probably the only Caltech graduate with that combination. Soon after completing his degree, Cornell University offered him a faculty position in the biochemistry department. Before coming to Ithaca, he spent a brief postdoctoral stint at Oxford University. Having only taken one autotutorial biochemistry class as a student, Dr. Feigenson essentially learned biochemistry by teaching it. Over the last 29 years, he has earned a reputation as one of the hardest working professors at Cornell for his dedication not only to research but also to teaching.

His current research focuses on how lipids spontaneously mix with each other in membranes and the role of cholesterol in controlling the different phases (e.g. liquid, solid-like, and liquid-ordered) in lipid bilayers. The Feigenson lab is much more of a chemistry lab than a biology one. Therefore, undergrads seeking a research position should have a strong predisposition and proficiency for chemistry. In other words, you must enjoy chemistry to work in this lab. Undergrads use a variety of chemical and physical techniques in their research. They typically measure lipid concentrations of samples and mix lipids together to generate artificial membranes. They also use fluorescence microscopy to track the location of fluorescently-labeled lipids in bilayers.

Dr. Feigenson is always eager to talk to undergrads, so feel free to contact him if you have any questions.