Hughes Mentor:  Siu Sylvia Lee

Department: Molecular Biology and Genetics

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Meet a Cornell Researcher – Sylvia Lee

Professor Sylvia Lee grew up in Hong Kong, but then moved to Houston, TX to attend Rice University. As an undergrad, Professor Lee did research on neurodevelopment in Drosophila. She said that her undergraduate research experience at Rice was similar to the current experience of undergraduates in her own lab at Cornell. She was paired with a post-doc, like beginning students in her own lab, to learn techniques.

After graduating from Rice, Professor Lee decided to stay in Houston to do her Ph.D. in cancer biology at the Baylor College of Medicine. She then did a post-doc at Harvard Medical School. After doing biochemistry research she wanted to go back to genetics so she decided to work on C. elegans, a worm, for her post-doctoral research. C. elegans was a good model system to work with because many of the genes and biochemical pathways in the worm are conserved in humans and it is extremely easy to grow and maintain. This is how she became interested in longevity and aging, which is what her current research focuses on.

Professor Lee then came to Cornell after her work as a post-doc. Many factors went into her decision of where to go such as the research environment. She commented that a normal university (like Cornell) is much different from a medical school or a research institute. The fact that her husband had a job at Cornell and that she could teach played a role in why she came here.

At Cornell, Professor Lee teaches a course titled “Regulation of Cell Proliferation, Senescence, and Death”, which is not directly related to her research. This makes teaching challenging because she has to learn a lot of new things on her own. However, teaching does broaden her view of science and there are times when she can apply what she is teaching to the work she does in the lab. She said that the two do “synergize.”

Professor Lee sees the future of biology in the next ten years being a lot of genomics research after the sequencing of so many genomes. She also sees a growth in interdisciplinary research. Although it does not relate directly to her own work, she also sees a lot more environmental research and how it relates to biology.

When undergraduates approach her to work in her lab she is looking for committed students that are looking to put in the time and effort. Her undergraduates work on projects as important as everyone else’s projects in the lab, so undergrads have to be excited and enthusiastic about research. Professor Lee also encourages undergraduates to do what they love, whether it is research or something else. She says not to do something someone else wants you to do because if you do, you will lack the motivation to succeed.

In her free time, which is few and far between, Professor Lee likes hiking, jogging, and gardening – things that Ithaca is good for. But, she finds research most exciting. Training people in research is very satisfying for her and it is nice to see people succeed and move on. The best part of research is finding something completely new that you weren’t looking for.

Undergraduate Research in the Lee Lab

After a year at Cornell, I was very keen to get into undergraduate biology research as soon as I could. My interests in biology were very broad at the time and so I browsed through several of the helpful faculty research packets kept in the Office of Undergraduate Biology, giving equal consideration to the research opportunities available in biochemistry, genetics and even microbiology. Among the detailed lists of research topics I came across one that said “Molecular mechanisms of how longevity is controlled in an organism”. While the concept of longevity research was new to me, I found it fascinating and immediately became interested in joining Dr. Sylvia Lee’s lab. While I considered several other labs, I eventually joined Professor Lee’s group in the spring semester of my sophomore year, marking the start of fruitful undergraduate research experience for myself.

The Lee lab studies the genetic basis of longevity in C. elegans and as such uses a combination of genetics and molecular biology techniques in carrying out its research. Undergraduates that are new to the Lee lab spend their first semester working on backcrossing a worm strain for the lab. This lets students learn how to work with worms and set up crosses while also learning to do PCR and gel electrophoresis that will together give them a good grounding in the basic techniques needed in order to work on their own project. After completing a backcross for the lab, I began working on a project to find new regulators of sod-3, a gene that is known to affect the lifespan of C. elegans. Given the nature of the project, I learned many additional techniques including RNAi, DNA sequencing, RNA extraction, RT-PCR and lifespan assays. As a project progresses and goes in new directions, you will undoubtedly get the chance to learn new experimental methods.

On a typical day in the Lee lab, my work is often divided into three categories. A good part of my time is spent at my desk just planning out experiments. Because we work with worms, which have a well-defined life cycle and grow at specific rates based on temperature, a lot of our experimental work is very schedule-based. Because of this, good planning is essential to making your lab work fit in with your other commitments. I also spend a good amount of time at the microscope, which is used to manipulate C. elegans. A lot of the experiments we do begin with the worms being set up under a microscope. We also use them to maintain strains of worms that we need and for scoring results from various assays. The remainder of my time is spent at the bench where all of the molecular biology work is done. This can range from setting up PCR reactions or gels to inoculating bacteria for an RNAi experiment.

While the majority of my time in the lab is spent on lab work, there is also a lot of interaction with other lab members. On a regular basis, I talk with Sylvia about any progress that I have made or if I need her advice on something that I am working on. Undergraduates also get to present to the lab group twice a semester on how their project is going and get feedback in return. The lab environment is also very relaxed and friendly. Some of my best lab moments are from the interesting conversations the group gets up to in lab’s kitchen. Because the lab is relatively small, you get to know everyone really well and this makes it easy to get help on something if you are stuck.

It’s been almost two years since I joined the Lee lab and, in that time I have had the chance to learn a host of experimental techniques and get valuable research experience. As my research project continues to progress into an honors thesis, I can say with confidence that choosing the Lee lab was a good first step towards my goal of becoming a biology researcher.

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

I first heard of the Lee Lab during the orientation week of my freshman year. I attended one of the research panel discussions hosted by the Undergraduate Office of Biology and one of the panelists was a senior working in Dr. Sylvia Lee’s lab. I was almost immediately attracted to the topic of her research – aging. I spoke to the panelist after the discussion and asked her about the Lee lab. She gave me the contact information of Dr. Lee and encouraged me to e-mail her for a position in the lab. Dr. Lee was very friendly and scheduled an appointment with me to talk about her research in greater depth. She informed me that although she didn’t have any opening in her lab at that time, she imagined that she would have some opening in the following year and offered me the position for next year. I gladly accepted her offer and looked forward to my sophomore year.

During the spring semester of my freshman year, I got an unexpected e-mail from Dr. Lee, saying that she had an opening in summer and wondered whether I would like to work for her during the summer. I immediately said “yes”, and started my undergraduate research experience that summer. I have worked in the Lee lab for two years now, including all the summers

My project is titled “Investigating the Roles of spt-4 and spt-6 in C. elegans Longevity.” The Lee lab has identified several novel longevity genes in a RNAi longevity screen two years ago, and spt-4 is one of these genes. spt-4 and spt-6 are known to work together to form a transcription factor complex in yeast, so we decided to study both genes together. In my project, I performed PCR to genotype the mutants, RNAi to inactivate the gene expressions, lifespan assays to analyze the lifespan phenotype, egg-prep to synchronize the worm’s developmental stages, and RT-PCR to monitor the expression levels of the genes I am interested in. I imagine that I will perform western blot and immunoprecipitation in the future to identify what proteins are interacting with SPT-4 and SPT-6 on a molecular level.

A typical day for me in my lab starts at 10 am. After arriving at the lab, I first look through my notes and identify what tasks I will be doing on that day. These tasks usually involve scoring my lifespan assays and other molecular experiments. I typically work until 12 pm, and take an hour-long lunch break. I would resume working until 4 pm, and leave the lab to go to Hughes seminars. Usually I would go home after the seminars to eat dinner and go back to lab at around 7 pm. On a typical day, I would finish all the experiments by about 11 pm.

Since I am working with living organisms, I have to compromise my schedule to accommodate the development of the worms. Although my schedule may seem demanding, I really enjoyed working in the lab. I think the sense of accomplishment I feel in my project really outweighs the demands. It is interesting to reflect upon how much I have learned through working in this lab and how much I enjoyed the problem-solving during the course of my research. In addition, the Lee lab members are all very supportive and helpful, and they make researching in the Lee lab a wonderful experience.

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

I first heard about research opportunity in the Lee Lab when I took Prof. Sylvia Lee’s BioBm437 Cell Proliferation and Senescence course. I really liked the way she taught and became interested in her research topic. I also met one of the graduate students in the Lee lab because he was my TA for Genetics. He also spoke highly of the lab so I sent Prof. Lee an email and inquired about any openings. After sending her my grades, she offered me an interview and decided to accept me. Although no courses were specifically required, knowledge of intro bio and genetics was pretty much essential for understanding my project. Also, familiarity with making reagents and buffers as gained in intro chem. Labs is vital.

My typical day in summer starts the morning somewhere around 10am. I usually make a quick mental checklist of the things I need to do and then proceed to do the day’s experiments. Usually once every day, I check in with Prof. Lee to discuss results or future experiments. About 30-50% of my time is downtime in between experiments where I chat with lab mates, check email or read papers. I typically spend about 8-9 hours per day in the lab although that number can vary. Pressure to generate results is very high and there is always stress associated with the uncertainty of experimental outcomes.

The project I am working on is to generate an antibody against DAF-16. DAF-16 is a major downstream effecter of the DAF-2/Insulin signaling pathway that acts to control lifespan in C.elegans. DAF-16 is a member of the FOXO subfamily of transcription factors in C.elegans which share a monomeric 100 AA long “forkhead” domain that binds conserved DNA segments. When DAF-2 is deleted or suppressed, DAF-16 translocates to the nucleus and modulates the transcription of a variety of genes that can lead to a several fold extension of worm lifespan.

My goal is to generate a recombinant DAF-16 CT protein fused with the 6-His tag. The DAF-16CT has only the C-terminal of the protein and lacks the forkhead domain. Using DAF-16CT as an antigen will allow us to generate an antibody specific for DAF-16 that will not bind to other FOXO transcription factors. Upon expression of DAF-16CT, we will use a nickel chromatography column that binds to the 6-His tag to purify DAF-16CT. We will then send the protein to a company for antibody generation. This antibody will allow us to better visualize DAF-16 and study its localization within the cell as well as conduct Co-IP to determine DAF-16’s interaction with other proteins.

Meet a Cornell Researcher: Sylvia Siu Lee, PhD

Dr. Sylvia Lee went to Rice University for her undergraduate years, which was when she decided she would like to pursue science. She spent 6 months after graduation working in fly lab and then entered graduate school at Baylor. Having spent much time in Texas, Dr. Lee decided to do her postdoc in Boston. Moving to Ithaca just three years ago has been quite a change, but Dr. Lee and her husband enjoy the quiet serenity of Ithaca in comparison to the hustle and bustle of an urban setting. When asked what specifically attracted her to our institution, Dr. Lee attributed it to Cornell’s research strength and flatteringly, us undergrads.

Dr. Lee values student interaction but at the same time, focuses very much on her investigation into the biology of aging. When asked what she thought about the hype surrounding human longevity research, Dr. Lee does not think anyone is seriously thinking of applying the biology of aging to extending lifespan. Rather, she believes the appeal lies in the theory that the mechanisms behind aging are the same behind disease formation. She points out that numerous diseases plague the aged, indicating that perhaps there is a common root behind old age and disease, specifically cancer.

Undeniably, Dr. Lee’s research is fascinating, but there is definitely more to science than simply conducting experiments. Conferences, presentations, collaborations, and more, allow research to grow beyond what we can do alone. Social interactions are essential, and society may always view individuals differently based on gender, race, or age. Therefore, I wondered whether being a woman would have any effect, positive or negative, on a researcher. Dr. Lee gave some thought to this before answering and overall concluded that there may be only a slight disadvantage. She has observed that men tend to be more confident when they speak in public, and are therefore able to “gain an audience easier.” She has seen that men tend to be more able than women to project authority. The result is being able to convince others of the importance of their research in a presentation or in a grant. Of course, Dr. Lee notes that this depends on personality as well. Some women are definitely more assertive whereas, others are more soft-spoken, which Dr. Lee admits she is herself.

When asked how she overcame this, Dr. Lee tells me she owes it to her advisor and mentors during her postdoc training. She stressed the importance of effective communication in research, and how her mentors would go through trial runs with her before presentations. Dr. Lee’s view is that “Your research must be good [but it is also] how to tell the story.” How to present one’s research, both spoken and written is vital. The take-home message then is for women scientists to be more outspoken in the field, exude more confidence, and of course (and this goes for both genders), always work on improving communication skills.

An Interview with Dr. Sylvia Lee

Dr. Sylvia Lee is an assistant professor in the department of molecular biology and genetics. Her research involves using C. elegans as a model genetic system to investigate how aging and senescence are affected at a molecular level. Dr. Lee originally grew up in Hong Kong, where she completed her high school education. In 1990, she moved to the United States and enrolled at Rice University in Houston, TX. Although she encountered a very different culture in the States, she found that it had many new and unique experiences to offer. As a result, she did not find the transition as difficult as she had expected. After finishing her undergraduate education at Rice University, Dr. Lee obtained her Ph.D. at the Baylor College of Medicine and did her post-doctoral work at the Massachusetts General Hospital. This is where she first began her work on C. elegans and longevity. In 2003, Dr. Lee decided to accept a position at Cornell University. Cornell appealed to her because of its large resources and distinguished faculty. Her decision was also made a little easier by the fact that her husband, Dr. Robert Weiss, had also been recently accepted as a member of the Cornell faculty.

Over the past two years the Lee lab has been making steady progress towards its stated goals. Last year it published a genome wide RNAi screen, which identified nearly ninety genes that extend the lifespan of C. elegans. Dr. Lee now plans to focus on characterizing some of the genes and their effects in greater detail. She also plans to see how conserved the mechanisms controlling longevity are in higher organisms. The main benefits of her research will be in better understanding and treating age-dependent diseases such as cancer, neurodegeneration etc.

Dr. Sylvia Lee

In 2003, Dr. Sylvia Lee joined the Cornell faculty as an Assistant Professor in Molecular Biology and Genetics. Originally from Hong Kong, Dr. Lee came to the United States to complete her undergraduate studies in Biochemistry at Rice University. After graduating, she attended Baylor College of Medicine for graduate school and graduated in 1999 with a Ph. D in Molecular Virology. At Baylor, her research focused on a molecular mechanism of transformation involved in an oncogenic virus.

Dr. Lee first became involved with Caenorhabditis elegans, the model system she works with at Cornell, during the three years she spent at Massachusetts General Hospital on a Postdoctoral Fellowship. Her research dealt with the genetic determinants of longevity in C. elegans, which has also become the main focus of her lab here at Cornell. While the Lee lab is searching for genes that will affect lifespan in the model system they work on, they hope that their findings with be beneficial to humans as well.

Dr. Lee is currently studying the mechanism behind an insulin-signaling pathway, which has been implicated in the process of aging in previous research by other labs. She believes that aging is the key to finding out the causes of many age-dependent diseases, such as cancer. Dr. Lee feels that by working to understand a much broader topic, she can tackle many more specific problems indirectly.
Undergraduates are more than welcome in Dr. Sylvia Lee’s lab. She considers them essential to science and acknowledges the fact that they can positively contribute to research. She especially admires their enthusiasm towards learning about the scientific process. Dr. Lee hopes that as a mentor she can give students a good impression of science and encourage them to incorporate it into their careers.