Hughes Mentor:  William Brown

Department: Molecular Biology and Genetics

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Interview with professor William Brown

Professor William/Bill Brown is a Professor of Cell Biology in the Department of Molecular Biology and Genetics at Cornell University. His life is interestingly filled with adventures. Originally from Long Beach, California, he was mainly interested in sports and thought he would be a professional athlete his whole life. In fact in his undergraduate program he majored mainly in English and Philosophy which is surprising considering that he is working in the scientific field right now; however this can not be considered as a waste of time, because these areas of expertise are very helpful and necessary, even in the scientific world.

Unfortunately he realized that he could not achieve his dream of becoming an athlete so he joined the military service. He was fortunate enough not to have to participate in the Vietnam War; so he quitted the army and spent 6 months in a meat packing factory. But he soon realized that he should do something better in his life.
So he continued his studying, but this time in the scientific field. He took a particular interest in cell biology which he found very inspiring. With his masters in Biology in hand, he joined a lab in the the University of Texas Southwestern Medical Center at Dallas in 1981, where he got his pHD in Medical Sciences. He then did his post-doc in Yale University and finally was appointed as a research faculty in Cornell University in 1985. He was enthusiastic to be here, because Cornell provides many opportunities of expanding the research, but also because people here tend to appreciate nature and family life.

In fact, he has been working on his current project for more than 10 years. His project is about the intracellular membrane trafficking and specifically about the tubules formation which occurs during the trafficking between the Golgi complex and the ER. This whole project started when in 1990, a group of people published a paper concerning an observation they made about the formation of membranes tubules that extend from the Golgi complex and endosomes and the sudden disappearance of the Golgi complex in the presence of BFA. When reading the paper, he became very interested in this event and decided to further investigate this phenomenon and understand its mechanisms. He is specifically focusing on the phospholipids-modifying enzymes in tubule formation and the role of these tubules in cell trafficking. He uses mainly green fluorescent imaging to study the behavior of the molecules and organelles and perform in vitro reconstitution of these tubules.

When speaking about research one could feel his excitement about the process of discovery that is available only with research, but also about its practicality and the continuous process of learning. I can not say the same thing when he mentioned the frustrations which could arise as well; especially when grants and papers to write accumulate. He enjoys his flexible schedule and can even practice his hobbies while at home; which are reading, gardening, and playing basket ball.

His lab is composed of post-docs, graduate and undergraduate students and each of them has their own responsibilities to assume. In fact he expects from them to be interested, excited about what they are doing and also passionate. He insists on the fact that graduate students should have creative thoughts. Undergraduate students, on the other hand, should have an independent thinking, and should also find out by themselves whether a research career would suit them or not; and the only way to do it, is simply to experience it. In fact he also would like them to think by themselves and not only apply routinely the procedures. They should show enthusiasm and passion as well and also practice their dexterity skills.

It was very interesting to talk to Prof. Bill Brown, because I not only learned interesting aspects about cell biology, but also about the faculty here in Cornell, and what a professor expects from us. However what Prof. Bill Brown mainly taught me is that it is never too late to achieve your dreams and proper goals in life.

A Day in the Life of an Undergraduate in the…..Lab

From my experiences working in the Biology Laboratory in college, I have started to like being in a laboratory environment, however, I was still unsure about what type of work I wanted to do. When I got into Cornell University, I began to be interested in doing research, so I began asking people questions about doing research and browsing the Biology Department website for faculty members doing research at Cornell. That was how I discovered Dr. Brown’s research project. I emailed him and several other faculty members about my interest in doing research with their lab groups. Most of the faculty members had their labs filled, but Dr. Brown and another faculty member invited me to talk to them about the possibilities to work with them. As I was discussing with Dr. Brown about this possibility, I found that his project was really interesting and he was a really friendly and easy-going professor. From then on, I began wanting to work with him. After a few more meetings to talk about some possible projects, I decided to work with him and fortunately, I have never regretted my decision.

Since our lab’s research projects revolve around cell biology, I had to read some cell biology textbooks on membrane trafficking and a lot of papers on research about these topics that were done in the past.

I usually come at around 9 in the morning, then I usually begin the day by checking my emails and making my schedule for the day. At first, there were not a lot of things that I could do before I began my project, but afterwards, I got pretty busy most of the days. I work with mammalian cells that are already cultured in dishes. Some of the cells that I work with come from human cancerous cells (HeLa cells), and from Chinese hamster ovary (CHO cells). Since they must be grown first before I can do experiments with them, I have to learn how to grow them first before I can do anything else. At first, I spent most of my days splitting these cells so they would not be overgrown. The most important thing that I learn from this is that I have been practicing how to work in a sterile environment and that involves a lot of ethanol. I practically have to spray ethanol to every flask or bottle containing solutions that I need to use in the hood where I work with the cells.

The techniques that I am using for my experiments are generally included as molecular biology techniques which include gel electrophoresis, transformation, transfection, mini-prep to extract DNA and many others. This project has taught me how to do a lot of stuff in the lab, I learn how to use fluorescent microscope which is far more sophisticated and cool than the regular light microscope. I feel gratified when I look at the cells that I work with after transfection with different genes and find that they indeed react to those. By working in this lab on this project, I also learn a lot about myself. I find that some of my characters become more obvious when I am working on experiments. I become more enthusiastic, serious and independent, but at the same time, I learn not to be ashamed to ask a lot of questions when I do not understand something. I also have experienced how tiring and time-consuming doing research is, and I do need blocks of time if I want to gain any useful results at the end.

Generally, the people in my lab and even the professor are very friendly and relaxed, but they do get quiet and serious when they start doing experiments. I learn how to get along with them and we do get along nicely. So, I think anybody who thinks that they are interested in research and wants to know if they are suited for it is eligible to work in a lab like ours. As long as these students are excited about doing research and having fun during special occasions, they should be interested in joining the lab, because besides doing research, we do a lot of other fun stuff too.

When I was in the lab during the school year, I was not be able to experience what it is like to be doing research full-time. I was always worried about completing my school assignments, or studying for my exams. As a result, I could not concentrate fully on doing my experiments and I always felt like going home to do my schoolwork. I was confused and always wondering if I was ready and would like to do research for a career. However, doing full-time research during the summer makes me realize that experiments take a lot of time and commitment. I learn to accept failures and manage my time better. My mind is focused on getting the best results out of those experiments without having to worry about schoolwork. Honestly, this is one of the reasons why I like doing research and being in the lab for this summer. The best advice that I can give to balance research and schoolwork during the semester is that people who really want to try doing research should set aside blocks of time after classes, preferably; otherwise, there will be no time to do any complete experiments. I still think that schoolwork should be the first priority before research, unless you are a graduate student probably. Consequently, this is where excellent time-managing ability is very important for students who want to juggle between research and schoolwork.

Lastly, I am very pleased that I decided to spend my summer here doing full-time research. I get to know all the people in the lab, and as it turns out, they are much nicer than I expected. I am also grateful that I decided to choose to work in this lab, because I still get to check emails, play my computer (not so often though) and chat with other people while waiting for incubations to end during my experiments.

A Day Spent in the Brown Lab

I thrive off of organization. At 11 am, I will stroll into Biotech. Then, of course, I will (1) split my cells; (2) extract DNA from my innoculation; (3) set up restriction enzyme digests. Last night, I started an innoculation—the transfer of bacteria from an agar plate with a selective marker (typically, an antibiotic) to a liquid media. By 11:30 am, I would have given my bacteria a solid 13 hours to grow in luria broth.

The Hughes Scholars Program has funded me to spend a summer in Ithaca. Although I relentlessly make detailed schedules and to-do lists, my research has been scattered from early mornings to late afternoons or vice versa (although infrequently). Sometimes, a quick rendezvous with my cells during the weekends were in order, and by rendezvous, I mean splitting my high-maintenance cells.

Working in the Brown Lab this summer has opened my eyes to the flexibility of research. It takes a certain person with a certain passion to conduct small experiments throughout the day. Personally, I was unprepared for a series of cloning failures, which began at the end of the spring semester and into a good portion of the summer. But today, it will work, or so I tell myself. Last week, Elysa Goldberg, a recently crowned Ph.D. in the Brown Lab, sat me down after having witnessed my somewhat discouraged state, and said, “Let’s make it work.”

After a pep-rally-esque talk, like one which brings back fond memories from high school, I started to cross items off of my list. This would have been the x-teenth time I have attempted this cloning, but this time, I also outlined every step taking careful note of precautionary measures I would take to ensure the greatest chance for a successful clone.

The potential for a successful clone can be defined by the presence of colonies. And, I had colonies that I sent to be sequenced yesterday, the results of which dictate the fate of my cloning. Now, however, I am performing a double restriction enzyme digest, which simply translates to cutting the plasmid that I have obtained with two restriction enzymes, which result in two fragments, the vector backbone and the insert of interest. A quick gel electrophoresis run should yield two bands if the cloning had worked.

After two hours of waiting for the restriction enzyme digest and then another hour for the gel to run, I take a quick glance at a photograph of my gel. The gleaming white bands amid the pool of black ink revealed two bands in three of the nine bacterial colonies I’ve picked.

Although Dr. Goldberg is no longer in the Brown Lab, she will be pleased to know that both of my cloning experiments have worked. These moments of success alongside the many moments of small failures are what define the research experience, and I could not be more satisfied.

An Interview with Dr. William Brown

Dr. Brown is a Professor of Cell Biology in the Department of Molecular Biology and Genetics here at Cornell University. A native of Long Beach, California, Dr. Brown has forgone the beautiful weather of sunny southern California to pursue his research career. However, becoming a biologist was not his original intention. After a stint in the U.S. Army Reserves, Dr. Brown spent 6 months in a meat packing factory working the hot dog line. This experience gave Dr. Brown a very strong sense of what he did NOT want to be doing for any extended period of time (a realization that Dr. Brown suggests everybody should experience first-hand). So, he decided to try his luck on the football team at a local community college. However, Dr. Brown’s distaste for being hit by bigger and stronger guys led him to relinquish his football ambitions. The California State University at Long Beach was Dr. Brown’s next stop, where he began pursuing interests in English and philosophy. It wasn’t until his senior year, after a taking a great cell biology class, that Dr. Brown found a home in the wonderful world of biology and decided to obtain a master’s degree in the field. Dr. Brown then went on to receive his Ph.D. in Medical Sciences from the University of Texas Southwestern Medical Center at Dallas in 1981, under the mentorship of Bill Snell. After graduate school, Dr. Brown found a Postdoctoral Fellow position in cell biology at Yale University, working with Marilyn Farquhar. In 1985, Dr. Brown came to Ithaca and joined the faculty at Cornell University. Dr. Brown also had the honor of being a Visiting Scientist at the Scripps Research Institute in 2003.

Dr. Brown’s research interests focus on the mechanisms of mammalian intracellular trafficking and organelle biogenesis, as he is quite intrigued by the question: how does all the “stuff” inside a cell get to where it is supposed to be? More specifically, Dr. Brown is investigating the phenomenon of membrane tubules that extend from the Golgi complex and endosomes. The existence of these tubules is very well documented for a variety of organelles; however, their function is not well understood. Therefore, Dr. Brown is seeking to elucidate the role that these membrane tubules play in membrane trafficking. Much work is being put into determining how these tubules form, and recently Dr. Brown’s laboratory has focused on the role of phospholipid-modifying enzymes in tubule formation. Two main approaches, including in vitro (cell free) reconstitution of the tubule formation process and identification of pharmacologically interesting inhibitors of tubule formation, are being used. Since the current understanding of membrane tubules is in its infancy, Dr. Brown’s research is poised to have far reaching implications, as it seeks to understand a fundamental process of cell biology. For a more detailed summary of Dr. Brown’s research efforts and a list of recent publications, see Dr. Brown’s homepage through the “Faculty” link on the Department of Molecular Biology and Genetics website (www.mbg.cornell.edu).

Very recently, Dr. Brown has added a new study to his repertoire: the cellular mechanisms of lipid storage. With obesity now being considered an epidemic both in the United States and on the global stage, understanding how cells store fat is becoming a pressing issue. It has been shown that virtually any somatic cell can be induced to store excess lipids in culture by the simple addition of excess lipids to the culture medium. From an evolutionary perspective, this propensity for fat storage makes a lot of sense. For the greater part of history, food has been quite scarce for most of the animal kingdom. The ability to store energy in the form of fat when food is available, for use during less prosperous times, has provided a strong evolutionary advantage. However, as times have changed and this scarcity of food has disappeared in most of the developed world, obesity has become more and more prevalent. At the cellular level, excess lipids are stored in what are commonly called lipid bodies. These lipid bodies form between the lipid bilayer of the endoplasmic reticulum and bud off as globs of fat surrounded by a lipid monolayer. As a matter of fact, cholesterol esters are stored there as well. The process by which a cell regulates the storage and release of the energy contained in these lipid bodies is poorly understood. Dr. Brown’s laboratory will begin probing these issues in order to better understand the cellular mechanisms of excess lipid storage.

Unfortunately, Cayuga Lake is not the Pacific Ocean, which prohibits Dr. Brown from hanging ten when he is not in the lab (not to mention the difference in climate), as he might be if he were still on the west coast. Since, surfing isn’t an option, you may catch Dr. Brown shooting some hoops or at least cheering on his hometown favorites, the LA Lakers, during his free time. The hike down Treman Gorge is one of Dr. Brown’s favorite Ithaca experiences, and he suggests that every Ithacan should try it. Dr. Brown also co-teaches BioBM 636 alongside his colleague Dr. Anthony Bretscher, which is a great course in advanced cell biology. To talk to Dr. Brown about anything from cell biology to surfing, you can contact him at wjb5@cornell.edu.

An Interview with Bill Brown, Department of Molecular Biology and Genetics

Bill Brown, professor of cell biology here at Cornell, hails originally from Long Beach, California. Before deciding on a career in biology, he spent time in the Army Reserves, community college, and tested the waters of philosophy and English at Long Beach State University. Although he always had a natural interest in science, it wasn’t until taking a required biology class that he got really interested in the subject and truly enjoyed it. It’s refreshing to meet a successful scientist who found their focus relatively late! The class motivated Brown to switch his major to biology and take all the required courses in his last two undergraduate years.

He stayed at Long Beach to pursue a masters degree in cell biology and joined the lab of the professor who taught that life-changing introductory bio course. It was during this time that he learned relevant techniques like electron microscopy and published his first paper. He also had his first taste of teaching and started considering life in the academic world.

Unsure of what would come next, Brown applied to graduate schools after he received his masters and also got community college teaching credentials in biology. He decided to go to graduate school at University of Texas Southwestern Medical Center at Dallas. He says at the time it was the perfect place for him: low-key, relatively new and well-funded, and there were many really talented people ready to burst onto the scene. After completing his PhD, Brown did postdoctoral work at Yale Medical Center and then came to Cornell University in 1985.

The Brown Lab works on the secretory pathway, particularly on membrane tubules that play a little-understood role in trafficking between organelles. When we learn about intracellular trafficking, we generally only hear about coated vesicles pinching off from the Golgi apparatus and fusing with their target organelles, specified by their coat proteins. But that is really only part of the story. The Golgi membrane also forms long, thin, uncoated projections that separate off and deliver cargo. It is known that when vesicle budding is chemically inhibited, the cell massively increases its production of membrane tubules. This suggests that the two transport systems are interrelated but it is not understood how. Looking for answers, the Brown lab is investigating the molecular mechanisms that activate and regulate the formation of these mysterious membrane tubules.