Author Archives: Michael Wen

I have had one of the most worthwhile experiences in a long time. I got to continue to work full time in a lab that I love, meet amazing faculty speakers with all different experiences, and really work on my skills as a communicator of science. These 8 weeks have gone by so fast and I can’t believe how much I have accomplished in such a short amount of time.

Even though I was not able to clone and successfully amplify all the genes I wanted, I was able to get promising data for not only my project but another project my lab is working on. I was able to deepen my understanding of developmental biology and have begun to truly love the topic. I am so thankful for having Dr. McClay and Ray be such amazing mentors and guide me throughout my 8 weeks and hopefully the rest of my undergraduate career. They have both given me the reigns on my own project and what I want to do from very early on and I am so grateful that I was able to get so much autonomy when doing my experiments because I grew so much from it.

The faculty speakers have also broadened my knowledge of the possibilities after college as well as the importance of things you usually won’t associate with science. Science communication and networking was brought up on many talks and I am so glad that I got to learn ways to communicate my science better and tips to network with other people in the sciences and form collaborations. In fact, I hope to continue to post on my science-specific Twitter account (follow me @Michael_Wen_) as well as participate in more science outreach like how I helped out at the Eno River Festival booth for the NC Herpetological Society. I actually applied to be a tour guide for the Lemur Center to take concrete steps to improving my network and science communication.

After hearing all the faculty speakers and realizing that I love being in the lab, this experience has affirmed that I want to continue doing research for the rest of the time I am at Duke and hopefully go into the route for academia once I graduate. I am so happy how I now have a better understanding of what I want to do in the future and what I don’t want to do.

Thank you so so much to Jason and Dr. Grunwald for being such great mentors and for planning such an amazing program for up and coming scientists. Thank you to all my fellow peers for making this summer such an enjoyable one.

Dr. McClay, my PI, during the BioCoRE Symposium Poster Session

Ray Allen, my graduate student mentor, at the BioCoRE Symposium Poster Session

Throughout the past 7 weeks, the research fellows have had the great privilege of listening to some amazing faculty speakers. From Dr. Nowicki investigating bird song to Dr. David collecting fecal matter for microbiome analysis, I have thoroughly enjoyed listening to the exciting research Duke faculty are doing and how they ended up doing research. One specific talk titled “Epigenome editing in neurons with dCas9 fusion protein” by Dr. Anne West really caught my interest because of both the science and the life lessons shared during the one hour she had with us.

Dr. West spoke about the changes in gene expression when neurons are fired and how the environment can play a role in DNA methylation which results in a changes in the epigenome. She talked about using the new technology of CRISPR-Cas9 to aid her research and emphasized that research is heavily based on the tools available at the time.

Although I found her science very interesting, her final note was what really stuck with me. She shared with us her lab’s mission statement which is:
“To answer vigorously defined questions,
To reveal something new about the brain,
To enjoy the process of discovery.”

These statements allowed me to reflect on my own choices when doing research. The first statement about answering questions emphasizes both the importance of asking good questions and having the resilience to answer them. The second statement highlights the importance of doing novel research rather than repeat experiments. The third statements underscores the fact that research needs to be fun and it is pointless to do something that isn’t. Research consumes a lot of time, energy, and resources so it is important to enjoy the process. These statements have made me realize that research is probably something I do wish to pursue because I enjoy spending time in the lab and asking and finding answers to relevant questions.

Dr. West was an amazing and inspirational speaker and I hope that I can take the lessons she shared and use them to motivate me in my path to pursuing research in the future.

Sea urchin embryos show a great affinity to replace cells necessary for normal development through a process called transfating in which cells in the embryo express genes of other cells to compensate for the removal. Specifically, the removal of primary mesenchyme cells (PMCs) which are crucial to the development of the skeleton triggers non-skeletogenic mesoderm (NSM) cells to reprogram in order to express genes found in the PMC gene regulatory network (GRN). A possible explanation is that the PMCs provide a signal to the surrounding NSMs that inhibit NSM transfating. This study seeks to determine 1) which genes are expressed in the PMCs and 2) what signal the PMCs provide to inhibit NSM transfating. Through in situ hybridization experiments using newly synthesized probes from a candidate gene list, we hope to determine which genes are PMC specific. Using in situ hybridization and drug inhibitor treatments, we test for ectopic cell reprogramming in order to determine the specific signaling molecules from the PMCs to inhibit NSM transfating. This study can broaden our understanding of the signaling molecules crucial to normal sea urchin development.

This past week, I listened to multiple people talk about their amazing projects. From using CRISPR/Cas9 to alleviate symptoms of muscular dystrophy to stress between male baboons, I have thoroughly enjoyed hearing about the research my peers are doing.

The one project that really peaked my interest was Sweta’s project titled “Epistability: Transgenerational and Environmental Effects on Plant Development.”

Sweta is looking at early plant development in the model organism Arabidopsis (which she called Dobby) and how the epigenetic changes can be inherited (which is very much a Lamarckian idea). Sweta is looking at the effects temperature has on growth, knowing that Dobby grows better at 22°C compared to 10°C. She has two aims: looking at the stability of the transgenerational effects and looking at the stability of the genotype. She is mainly working on her first aim the summer in which she is looking at 3 generations of plants treated at both hot and cold temperatures (see figure 1). When I asked her what she expects from her data, she said that she expects the parental environment to have the most effect on the offspring compared to the grandparents.

I found this topic extremely interesting because it seems very much like Lamarckian evolution rather than Darwinian evolution. I entirely believe that the environment has a strong effect that can be passed on from parent to offspring, especially after doing a field work experiment with a graduate student in the Donohue lab (the lab Sweta works in) on niche construction as a method to cope with drought. The idea that a phenotype in addition to a genotype can be passed down is very exciting considering we all express genes differently, although we have many of the same genes.

I final thing I was very impressed by was Sweta’s use of the board and presentation because she clearly knew what she was talking about and was able to demonstrate it well using only a section of the already limited space.

Figure 1

Since January, I have had the privilege of working in the McClay lab on a project involving the transfating of cells in the sea urchin embryo. As I begin my journey into science research with all the possibilities ahead, I felt it to be important to talk to someone who can look back on their research career to share some insight on being a scientist. Who better to talk to about his experiences than my PI, Dr. Dave McClay.

Dr. McClay began his journey in higher education at Pennsylvania State University where his father taught as a professor. He enjoyed many subjects, but biology just seemed to interest him slightly more. However, biology can range from molecular biology to evolutionary biology to ecology. So how did he end up in developmental biology? That would be thanks to his professor who recommended he look into developmental biology which he later fell in love with. He then went to the University of North Carolina in Chapel Hill for graduate school because he was offered a fellowship. After receiving his PhD, he spent 5 months at the University of Chicago working as a postdoctorate associate before getting a phone call to interview at Duke. He flew to Duke, had an interview, gave a seminar presentation, and the rest was history.

One question Dr. McClay often gets asked is why sea urchins? How did he get into using sea urchins as a model organism? He said that when he was in graduate school, he did a research project in Bermuda. This was the gateway to his desire to work at a marine lab every summer and he has worked in one ever since through an NSF grant which allowed him to work in Bermuda for 18 summers, Woods Hole for 12 summers, and France for another 18 summers. When asked which marine lab location he prefers, he says he loves all of them for different reasons: diving for your own animals in Bermuda, interacting with world-class scientists in Woods Hole, and being by the beautiful ocean in France.

One aspect of his job that he really enjoys is teaching. He began teaching anatomy to nursing students which is when he realized he loved teaching. This is the reason he knew he wanted to go into academia, so he could do the two things he loves: research and teach. He currently teaches 2 courses for undergraduates (Cell Biology which I am taking next semester and Developmental Biology) and 3 courses for graduate students (a module on developmental biology, a module on gene regulatory networks, and a developmental biology colloquium).

For my final question, I asked if he had any words of wisdom to share to someone beginning their journey into science research. He said that you should choose something that you love to do but be aware that you need to work hard as well because “it’s not a sprint but a marathon.” There are a lot of difficulties in science research but there are so many benefits as well and you just have to keep pushing through the hard parts for those benefits.

He ended our conversation with a phrase that really resonated with me and I will always keep in mind: “research is a career where the mind matters a lot so think, be creative, solve problems.”

David R. McClay, PhD (aka Uncle Dave)

What happens when you remove cells essential for development? How can cells detect changes around them in order to change their gene expression. Why are these questions even important?

Ettensohn and McClay show that the removal of skeletal cells from the sea urchin embryo causes non-skeletogenic mesoderm (NSM) cells to transfate in order to take on the role of the missing skeletal cells. Ettensohn et al. showed that a skeletal cell specific gene is expressed during the process of transfating because it plays an important role in the gene regulatory network in the skeletal cell lineage.

However, we still do not understand exactly how the skeletal cells suppress NSM transfating. Therefore, in the McClay lab, I work on a project to explore the question of how the embryo recognizes and regulates cell loss in the sea urchin, Lytechinus variagatus. In order to do so, I will be performing in situ hybridization experiments on a list of candidate genes expressed in skeletal cells in order to verify their expression. I have already designed and ordered primers that will be used to clone genes through polymerase chain reaction (PCR) of the sea urchin’s cDNA. The genes will then be used to synthesize RNA probes which will be used for the in situ hybridization experiments.

I will also be using drug inhibitors to see if there is ectopic (abnormal) cell reprogramming in the sea urchin embryo. This will be done by treating developing embryos at different time points with a drug inhibitor and performing in situ hybridization experiment. By inhibiting certain signaling molecules, I would be able to see whether or not the signaling molecule plays a role in the embryos recognition of skeletal cell presence.

These are my current aims for the summer, but I already have so many more questions popping up from preliminary data and reading the literature that I hope will guide me in the coming weeks and into the future.

For anyone who is confused about my title, here is a meme for your reference.