Hughes Mentor:  Jun Liu

Department: Molecular Biology and Genetics

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A Conversation with Dr. Jun Kelly Liu

There are many paths towards a career in research and, as in Dr. Jun Kelly Liu’s case, they can even involve crossing international borders. Born and raised in Nanyang, China, Dr. Liu studied Biology as an undergraduate at Wuhan University in China. Thanks to an exchange program between the United States and China, she got the chance to come to Cornell, where she earned a PhD in Biochemistry, Molecular and Cell Biology after working in Dr. Marianna Wolfner’s lab. From there, Dr. Liu went on to do postdoctoral work at the Carnegie Institution of Washington’s Department of Embryology before returning to Cornell in 2001 where she is currently an Assistant Professor of Molecular Biology and Genetics.

Dr. Kelly Liu’s lab uses C. elegans to investigate two different research areas. In one area, they study the basis of cell fate specification in the mesodermal development of C. elegans. This involves both forward and reverse genetics approaches to discover mutants and then investigate the biochemistry behind their mesodermal phenotypes. The lab’s second research focus seeks to answer the question of what roles nuclear envelope proteins have in early development. This research area was sparked by Dr. Liu’s earlier graduate work and has applications towards understanding muscular dystrophy and even premature aging. Given her research interests, Dr. Liu feels that C. elegans is the perfect organism to work with given that a lot is known about cell lineages in the organism and how easy it is to implement genetic techniques like RNAi or use GFP markers.

After completing her postdoctoral work, Dr. Liu said that she was firmly decided on going into academia. She enjoys the challenge of doing experiments herself and is passionate about transmitting her enthusiasm about biology to undergraduates through teaching. Today, she not only teaches BioGD 385 – Developmental Biology to undergraduates at Cornell but also offers BioGD 689 – Cellular Basis of Development to graduate students. In addition, she advises a group of biology majors and eagerly accepts undergraduates into her lab, which she finds to be a continuous source of inspiration for her.

With her mind set on academia, Dr. Liu’s choice to return to Cornell as a professor as opposed to exploring other institutions was also a firm decision. She found that her time in the Wolfner lab was very enjoyable and this helped her quickly realize that she liked the way biology research was done at Cornell. As a foreign national, Dr. Liu’s other alternative would have been to return to China, but she admits being averse to the option. Not only did she like the way research was done in the US, she felt that research in China was entrenched with a lot more personal politics. While she knew that she could prove herself in the US scientific community, she worried that her success in research in China would not just be about doing good science. Although she believes that the situation for biology researchers is improving in China, she does not envision going back to her home country to do research in the near future.

Dr. Kelly Liu was also keen to stay in Ithaca’s beautiful and safe environment that has proven ideal for raising her 7 year old daughter. She strongly prefers the quiet countryside of upstate New York to the urban environment of Baltimore, where she did her postdoctoral work. In this way, Cornell has provided her with the perfect balance between her research career and personal life.

When asked about whether she had considered other career paths, Dr. Liu confesses that she cannot imagine herself doing anything else besides research and teaching. She notes in passing that, from her beginnings in China, her career goal has always been to do something she loved. Given how far she has come, her philosophy is definitely one all college students should try to achieve.

A Day in the Life of an Undergrad in the Liu Lab

How I found my lab

As an incoming freshman, I had no idea what to look for in undergraduate research. My only preconceptions stemmed from older students who were already in college or from Pre-med books that continuously stressed the importance of becoming involved in research. With all this in mind, I set out on my search for work in a lab during orientation week while my hallmates were busy unpacking and getting settled in their new dorms. I checked the Cornell website everyday for new postings from professors seeking lab assistants, and while I suspected that being an assistant really had nothing to do with actual research, I felt like this was the best way to start. I sent out my resume to several molecular biology, genetics, and vet school labs, as I didn’t find plant or evolutionary biology to be interesting at the time. I remember that I was asked to come in for about six interviews during that week, and during each interview, I felt incredibly overwhelmed, as I was questioned by often daunting professors or grad students.

When I found myself at Professor Kelly Liu’s office, however, I was immediately struck by her ability to make me feel comfortable, even though she knew that I had absolutely no previous experience in lab. Furthermore, Kelly was able to excite me about her research and I quickly picked up on her fondness for the members of her lab, two things that could not have been said about other labs that I had visited.

What I work on

Though I work in a C. elegans lab, my daily work does not involve the direct manipulation of these nematodes (I did, however, work with C. elegans during my very first semester of research, which was really a transitional stage between being a lab assistant and having my own project). Because the main technique that is used in my research is the yeast two-hybrid system, I spend most of my time working with the manipulation of DNA as well as yeast, although the genes that I study are found in C. elegans and my results characterize how these proteins function in the nematode.

What techniques I use

For the first two semesters of my main project at the Liu Lab, I focused primarily on obtaining fusion constructs. Though it was a rather tedious procedure, I became familiar with several techniques and eventually became very comfortable with performing them, as several tries were usually needed to obtain and verify each construct – these techniques include digestions, gel electrophoresis, DNA purification, setting up ligations/controls, bacterial transformation, and DNA minipreps.

After obtaining my constructs for the yeast two-hybrid system, I learned how to transform yeast, set up matings, and streak out colonies. A thorough analysis of my data suggested several negative interactions for my proteins of interest, and consequently, I conducted Western Blotting to see if my proteins were being expressed properly. My preliminary results show that they are, but I plan on performing Western Blotting once more to confirm.

A Day at the Liu Lab

I struggle as I open my eyes and shut the alarm next to me. It is 8:30 already and I have to be in lab at 9:30 to remove my bacterial cultures from the shaker. They cannot be in there for more than 18 hours; otherwise, the whole week’s worth of work is gone.

I run out the door with coffee in one hand and my umbrella in the other. It is one of those rainy days again, in the midst of July! Fifteen minutes later, I’m waiting for the elevator in the Biotech Building. Because of all the recent renovations, it takes hours, or so it feels, for the elevator to come.

“Good morning, Herong. Good morning, Debjeet!” I greet my lab mates hurriedly as I put my bag on the desk and rush to the incubator to remove my tubes. They all look blurry, which is good because it means that my bacteria grew!

I open my lab notebook, and look at today’s list of things to do. Maintain my strains. Make glycerol stocks for my transformed bacteria. Plate my bacteria on RNAi plates. Check the genetic crosses. Talk to Kelly about my results from last week. Get the pictures off the scope for my presentation. And the list goes on. And all this has to be done by 4:30 pm, because one of my good friends is presenting today at the seminars, and I want to attend.

I decide to start with making my glycerol stocks. This is basically a procedure that would allow me to freeze my transformed strains for future use. I pour liquid nitrogen in a bucket and keep it ready for the last step of the procedure. I get eight cryogenic tubes with different-colored lids. And the hammering begins, literally! I have to hammer down all the lids on the tubes. I don’t know why these tubes do not come with their lids on, but that’s the way it’s done. I label all my tubes, and put on my gloves before I obtain the reagents needed. DMSO, check. LB, check. 1 mL and 100 mL pipets and tips. Check! I’m all set. I pipet the right amounts into these tubes and put them in liquid nitrogen. I carry the bucket and rush to the -80 ∞C freezer to transfer them. Ouch! Frost bite. I always forget to use napkins or a towel to avoid those things. It doesn’t matter now; I put my tubes in and go to get my RNAi plates.

I hate the 4 ∞C freezer. This is where we keep our RNAi plates. Again, I label them all. I pipette 200 mL of the respective cultures onto the plates. And I just leave them to dry. As I turn around to clean up my desk, Karima pops out of nowhere! Yes, time for lunch!

So what will it be today? Pizza or a smoked turkey wrap? I settle for the wrap and some fries. Trilium’s fries are just irresistible! I meet up with the rest of my friends as we discuss how the day has been for each of us and our plans for the rest of the day.

As I come back to lab, I notice that Kelly’s door is open. I knock and ask if she’s busy, and she welcomes me with a smile. We discuss the experiments of the previous week, what went wrong, what could have been better, and what should be repeated. We then take a look at the worms together in case I missed out on something interesting on those plates. Today, we are going to take pictures! That means I got results! It feels really good to actually see your experiments working. Kelly teaches me how to mount worms on slides, so that I can put them on the compound scope and take pictures. I practice on some of the worms and, before I know it, it’s 2:20 pm! And I still need to check my crosses and maintain my strains!

I have to pick adults from my plates and clone them onto new plates for the temperature sensitivity test. You see, the genes I am working with are temperature sensitive. They need to be maintained at 16˚C for the protein they code for to be expressed, otherwise the embryos die. So by transferring gravid adults to new plates and putting them at 25˚C, I can know whether the strain I'm working with is homozygote for my mutation simply by noting the presence of dead embryos. I find my pick, get ten freshly seeded plates, and turn on my microscope. It doesn’t take me as much time to pick anymore. Two months ago, when I first started working at the Liu lab, I spent the first three days doing nothing but picking worms. I remember getting nauseated and dizzy from spending so much time looking down a microscope at tiny squiggly things moving around. I used to poke the gel and squish the worms. Now, a gentle touch seems to be enough!

After cloning those ten plates, I perform new genetic crosses so that I can eventually produce mutants with specific markers. I move to the small room, where the fluorescent microscope is placed, and start looking for males with green pharynges. I have to find at least 20, 10 on each plate. I can only find 13! Crosses are pure probability. I decide to put them all on one plate. Then I pick three hermaphrodites for my mutant strains and plate them on the same plate. You see, C. elegans exist as hermaphrodites or males, with self-fertilization being way more frequent than cross-fertilization. So for every 10 males picked, only three hermaphrodites are added to increase the chance that cross-fertilization occurs! I put my plates back in the 16˚C incubator, and notice that it is 4:20 pm.

I rush back to my desk and pack my things. I guess maintaining my strains will just have to wait till tomorrow.

"Bye guys," I shout out as I hope that no fungi will infect my plates overnight.

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

I started working in the Liu lab the fall semester of my sophomore year. After exploring the research of various professors on the MBG website during the end of my freshman year, I wanted to work in Dr. Liu’s mesodermal development lab, because I was interested in the role genetics plays during development and was excited at the potential insight that such research would provide on genetic diseases in humans that affect mesodermally derived cells. I contacted Dr. Liu about joining her research team, and, luckily, Dr. Liu invited me for an interview and accepted me into her lab.

In the Liu lab, we use the soil nematode C. elegans as a model organism to study how different mesodermal cell types are specified during development. We are specifically focusing on the postembryonic M lineage, which gives rise to a variety of cell types such as body wall muscles, coelomocytes (macrophage like cells), and sex myoblasts. Our lab is working to identify and characterize genes that regulate cell fate specification in the M lineage using a combination of forward genetics, such as mutagenesis screens, and reverse genetics, such as RNA interference.

The techniques that I have been using in the lab are varied and include genetic crosses, PCR, fluorescence microscopy, bacterial transformations, and some antibody work. I personally did not have much lab experience before I joined the lab and learned many of these techniques from the graduate students and technician in the lab who were nice enough to teach me. Although previous lab experience would be helpful before working in the lab, it is not necessarily essential as long as you are willing to learn. Some basic knowledge of the techniques from classes, however, would come in handy. Some useful courses to take before working in the lab would be Introductory Biology, Genetics, and Biochemistry.

While I don’t really have a typical day because the techniques I use vary from time to time depending on the type of project I am working on, the majority of my day is devoted to running experiments. During the downtimes when waiting for PCR reactions to finish or during incubations, I spend my time reading papers written by the graduate students in the lab and also other papers relevant to my research. Often, it is easy to lose focus of the big picture of the research question when you are focused on your own particular sequencing reactions or how your own crosses are coming along. I find that reading about and discussing our progress with fellow lab members is an important and also exciting aspect of research that unites each lab member on a common ground in discovering an answer to a novel research question.

Researching during the summer has been great, because I have been able to fully immerse myself into experiments without the distractions of classes or prelims. During the school year, I feel that my experiments are discontinuous and sometimes rushed as I am trying to wrap things up between classes. Working during the summer has definitely enabled me to make progress on my project, and it is something I would recommend to anyone working in a lab.

The Liu Lab

Unlike most of the Hughes scholars, I have never been to the United States before. I study in Weill Cornell Medical College in Qatar, which is a branch of Cornell in the Middle East. I was awarded a summer research fellowship from my college; this is how I came to Cornell to work in the Liu lab. In our lab, we do genetic research on a microscopic worm called C. elegans. We are trying to study the process of cell differentiation in one of the tissues of the worm, specifically the mesoderm. General biology, genetics, and biochemistry are some of the subjects that I took during my first two years in college that were useful for understanding the research project. The technique I am using is called a mutagenesis screen, and the approach is called forward genetics. In other words, we expose worms to a chemical that mutates their genes, and then search for abnormal animals and try to figure out which genes were affected that gave us this particular abnormality.

A typical day in lab for me involves mainly independent work. I go in and look through my lab notebook to plan what things I can do for the day. Then I go to the incubator to get my worm plates with the mutants I have isolated during the first three weeks of lab work. Then I try to collect more data about the worms by observing them, counting them, observing their progeny, and sometimes mating them. Most of the work is done under the microscope. I also talk to people in my lab and ask them how to do a certain procedure or ask what they think should be done next.

From my experience in lab, I learnt more about the process of research and how each discovery or invention only comes after a huge amount of work done by many people who are all cooperating over many years. I also realized that I really enjoy being the first to reach or discover something. Students with curiosity to know more about science would really enjoy working in this lab. However, they should also have commitment and patience.

Working in a lab does not only offer the chance to learn about a particular topic in great depth, it also allows people to learn about other related subjects. Another exciting thing is getting to meet new people with different backgrounds and interests. In our lab, we have people from five different countries all working in one team. However, those variations add a special flavor to the lab and give us a lot of issues to discuss and enable us to learn more about each others’ cultures.

A Day in the Life of an Undergraduate in the Lab

I found my lab by using the online search provided by Cornell’s biology department. After looking through the list of faculty with research topics that were interesting to me, I picked a few and read their entire research descriptions. I then decided which of the research subjects I was most interested in, and contacted the professor whose lab I work in now about doing research in her lab. She agreed to arrange an interview, and then accepted me. I first contacted my professor the summer before my junior year (when I transferred into Cornell), but generally, I think most professors prefer taking freshmen and sophomores.

The lab that I work in focuses on development and genetics. We work with C. elegans, which is a small, transparent worm. It is very easy to work with, and much better to deal with than Drosophila, since it doesn’t fly away when you’re trying to do experiments with it. Many of the techniques used in my lab are ones common to most genetics and cell bio laboratories. This includes work with DNA - PCR, sequencing, and bacterial transformation, to name a few - as well as protein work, such as work with antibodies. We also do fluorescent microscopy, and probably many other things that I don’t know about yet. When I started working in my lab, I already knew how to do PCR, but over the past year I have been learning more and more new techniques.

A lot of the things that I learned in classes came in useful in lab, but many of them were not absolutely necessary. However, genetics and general bio are two classes that I think helped the most. Taking developmental bio helped me understand on a more broad level what my lab was studying, but I did not need it to do day-to-day experiments. Overall, I think the general rule is that if you don’t understand something, other people in lab will do their best to explain it to you.

Working in lab is drastically different during the school year than during the summer. During the school year, I always feel like I’m rushing somewhere, and it’s very hard to finish things. This can be frustrating, and you lose a lot of time on setting up your experiment and cleaning up after it, since you have to do it for every 2 hours of work that you do. It’s also a lot harder to put in extra time on weekends when you’re at a critical moment in your experiment if you know that you have a biochemistry test the next Monday. So if you do research, I definitely recommend spending at least one summer in your lab.

An Interview with Dr. Jun Kelly Liu

Dr. Liu was born and raised in China. After attending college at Wuhan University where she studied Biology, Dr. Liu participated in the CUSPA exchange program between China and the United States. As a graduate student here at Cornell University, she received a Ph.D. degree in Biochemistry, Molecular and Cell Biology using Drosophila as a model system for research on early embryonic development. Dr. Liu was very interested in the developmental processes in model organisms and decided to use Caenorhabditis elegans as her model organism while completing her post-doctoral research in Baltimore at the Carnegie Institution of Washington. She then came back to Cornell University and joined the faculty in the Department of Molecular Biology and Genetics.

The research in Dr. Liuís laboratory involves C. elegans, which is a free-living soil nematode. Adult worms are 1mm in length and are transparent, allowing all cells to be visible. C. elegans also exist as hermaphrodites leading to ease of keeping large populations. She finds this organism to be especially interesting it was the first genome to be fully sequenced and the entire cell lineage has been mapped. Since the developmental history has been determined, Dr. Liu is able to research how cells choose different fates and study gene function at single cell resolution. One focus of her lab involves the use of C. elegans post-embryonic mesoderm as a model system to study how mesodermal cell fates are specified. Another area of interest includes the study of functions of nuclear-membrane proteins in development. Mutations in nuclear membrane proteins cause a number of genetic diseases in humans, including muscular dystrophies, lipodystrophy, neuropathy, and pre-mature aging. The C. elegans nuclear envelope is similar to human nuclear envelopes.

Dr. Liu has and continues to do research with undergraduate students in her lab. She also teaches two classes here at Cornell, BOIGD 385: Developmental Biolgy and BIOGD 689: Cellular Basis of Development.

An Interview with Jun Kelly Liu

Even if you’ve decided that fruit flies aren’t going to be the model organism for your research, you can still worm your way into a lab in the biotechnology building. Dr. Jun Liu, on the 4th floor, has chosen the nematode Caenorhabditis elegans (C. elegans) to answer two big questions in developmental biology: 1) how a single fertilized egg can be differentiated and organized into a complex array of tissue and cell types that make up a multi-cellular organism, and 2) the role of the nuclear envelope in development.

There are several advantages to using C. elegans as a model organism in developmental studies. Firstly, the entire cell lineage of C. elegans has been mapped showing the life history of every somatic cell in the adult animal all the way back to the fertilized embryo. This was made possible because C. elegans is transparent and has a short life cycle, which allows investigators to label individual cells during embryogenesis with fluorescence and use a light microscope to observe the cells’ temporal, functional, and spatial development through an entire generation in just three days. Furthermore, with a complete genomic sequence, powerful genetic and molecular tools are made available to aid rapid identification and analysis of genes involved in cell development and differentiation.

Dr. Liu’s first research focus is the study of mesodermal cell development in C. elegans. In the M lineage, a single precursor M divides in a precisely reproducible pattern to give rise to the post-embryonic mesoderm composed of 14 striated body-wall muscles used for locomotion, 16 non-striated sex muscles for egg-laying, and 2 non-muscle cells. By making various mutations at genetic and molecular levels, Dr. Liu can discover genes that regulate the specification and diversification of the precursor M into different muscle and non-muscles cell types in the mesoderm. Further characterization of these genes can reveal the molecular mechanism underlying the cell division and fate specification of M lineage. These investigations will elucidate genetic and molecular similarities and differences in early animal development and also contribute to our understanding of the molecular basis of various cancers and genetic disease that affect mesodermal cells.

Dr. Liu is also interested in investigating the function of nuclear envelope during development. Specifically, she is studying the role of the nuclear lamina, a component of nuclear envelope, and its associated proteins in development of various genetic human diseases. It has been found that mutations in the nuclear lamina and associated proteins cause muscular dystrophies, lipodystrophy, neuropathy, and pre-mature aging. Several functions of the nuclear lamina, including chromatin organization, DNA replication, and transcription, are known, but a better understanding of the many functions of nuclear envelope in development is required to uncover the underlying molecular mechanisms of these disease in human.

Dr. Liu is an Assistant Professor of Molecular Biology and Genetics. She received a Ph.D. in Biochemistry, Molecular and Cell Biology here at Cornell University. After completing her postdoctoral research at the Carnegie Institution of Washington, she decided to return to Cornell in 2001 as one of the few female Asian faculty members in Biological Sciences. She teaches BioGD 385 – Developmental Biology, and BioGD 689 – Cellular Basis of Development. Her enthusiasm in teaching is not only apparent in the classroom, but also in her lab where she personally mentors each undergraduate student. She finds it especially gratifying to watch her undergraduate students grow and develop stronger fascination and passion for scientific investigation. So do yourself a favor and get to know Dr. Liu during your time at Cornell. Her energy and devotion for developmental biology is truly inspiring, even delightfully charming.

An Interview with Kelly Liu

Jun Kelly Liu received her B.S. degree from Wuhan University in China and her Ph.D. from Cornell. She did her postdoctoral research at the Carnegie Institution of Washington, Department of Embryology, and joined the Molecular Biology and Genetics department at Cornell in 2001. Dr. Liu is happily married and has a 5 year old.

The Liu lab uses the nematode, Caenorhabditis elegans as their model organism to study both cell fate and the function of nuclear envelope proteins during development. C. elegans is a very useful model organism because each cell’s lineage is known and can be traced back to the one cell stage. The Liu lab studies a specific lineage, the M lineage, to look at cell fate and specification. The M lineage includes cells that will form body wall muscles, coelomocytes (similar to macrophages), and sex myoblasts, the precursors to vulval and uterine muscles. The M lineage was chosen because it is simple, well defined, and not essential for viability of the worm. These traits allow for various genetic and experimental manipulations of the worm without harming overall fitness. The lab is currently interested in identifying genes involved in regulating cell division and specification within the M lineage. This research would not only contribute to the understanding of early animal development, but will also guide investigations into the causes and molecular basis of various cancers and genetics diseases that specifically affect mesodermally derived cell types.

The lab’s other focus is identifying the function of nuclear envelope proteins during development. The nuclear envelope is composed of three distinct components: the outer and inner nuclear membranes, the nuclear pore complexes, and the protein layer underneath the inner nuclear membrane, called the nuclear lamina. The lamina is mostly composed of intermediate family proteins A and B type lamins. These lamins attach to the inner nuclear membrane via association with integral membrane proteins. The lab uses C. elegans to study the in vivo functions of lamin and the lamin-associated nuclear envelope proteins during development. The C. elegans nuclear envelope is similar to human nuclear envelopes, but it has a much simpler composition, making functional studies much easier to perform in C. elegans. By studying these nuclear proteins, the lab hopes to better understand the molecular mechanisms underlying nuclear envelope-associated human diseases.