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This month’s Graduate Student Spotlight highlights Zhaolan Ding. A student in the Bell-Pedersen Lab, Zhaolan works on circadian clocks in Neurospora crassa. Learn more about Zhaolan and her graduate experience in this month’s Spotlight below.

 

Photo of Zhaolan Ding skiingZhaolan Ding

I am a fifth-year graduate student in Dr. Bell-Pedersen’s Lab. I grew up in Qingdao China, which is famous for its seafood and beer. I did my undergraduate study in Biology at the China Agricultural University in Beijing. I conducted research in Dr. Qun He’s lab, whose research focuses on understanding N. crassa circadian clocks. My work focused on the impact of the INO80 chromatin remodeling complex on the circadian oscillator. I chose to continue to work on circadian clocks in N. crassa in graduate school at the Texas A&M University with Dr. Bell-Pedersen.

 

What is the best advice you’ve been given?

Hope for the best, prepare for the worst.

What is one thing people would be surprised to know about you?

Even though I am from “the city of beer”, I am not good at drinking at all. About one third of a bottle of beer is enough to turn my face totally red.

What characteristics do you prize most in a colleague?

Respect, trust, support

Photo of Zhaolan Ding outsideWhat advice would you give to a new graduate student?

I want to share something based on my experiences and what I wish somebody would have told me when I joined graduate school.

The first thing is to believe in yourself. Self-doubt is a common feeling during graduate study since research is usually a slow and painstaking process, and because peer pressure can be tough. My suggestion is don’t compare yourself with your peers, and at the same time, try not to judge the research of others. We all have unique paths to success in our graduate study. We are from different cultures, we have different advisors, and even when in a same lab, we are working on different projects. Instead, focus on your own learning and growth. If we are doing better today than yesterday, better this year than last year, we are making significant progress and will attain our goal.

My second piece of advice is to communicate with your advisor and lab mates. Don’t hesitate to ask people if you have questions or need help.

What projects are you currently working on?

Previously our lab showed that the circadian clock controls rhythms in the accumulation of phosphorylated and inactivate translation initiation factor eIF2α, with the levels of phosphorylated eIF2α (P-eIF2α) peaking during the day. When P-eIF2α accumulates to high levels, translation initiation of most mRNAs is blocked. We identified CPC-3 as the kinase that phosphorylates eIF2α during the day. I hypothesized that there must also be a phosphatase that removes the phosphate, and that the phosphatase would be active at night. This would be predicted to lead to rhythms in mRNA translation with reduced translation during the day and increased translation at night. Consistent with this hypothesis, I discovered that phosphatase PPP1 levels accumulate rhythmically with a peak in the early night, and that cycling levels of PPP1 are necessary for rhythms in the accumulation of P-eIF2α. In cells mutated for PPP1, the levels of P-eIF2 are high at all times of the day, but the molecular clock still functions. I am currently testing if PPP1 directly dephosphorylates P-eIF2α. I am also using RNA-seq and Ribo-seq data to determine the impact of increased and arrhythmic levels of P-eIF2α on global mRNA translation.

What is the broader significance of your research?

The circadian clock has a major impact on human mental and physical health; therefore, understanding how the clock works and what it regulates is key to developing new therapies to treat circadian disorders, including metabolic syndrome and certain depressive illnesses. In addition, most drugs target proteins that are clock-controlled. Therefore knowing what proteins cycle and when they peak is critical to using these drugs effectively. While up to half of rhythmic proteins in eukaryotes arise from mRNAs that don’t cycle in abundance, the mechanisms of clock control of mRNA translation were not known. Our results demonstrating that the clock regulates the activity of a conserved translation initiation factor provides key insights into the mechanism of circadian regulation of protein abundance, and our current genome-wide studies will provide important information on which proteins are controlled by this mechanism.

What are the strengths of the Department of Biology at Texas A&M?

The Graduate Program in Biology has a wide range of research areas to choose from, including microbiology, plant biology, molecular biology, ecology, evolutionary biology, genetics, bioinformatics, developmental biology, and neurobiology, and faculty expertise in each of these areas. The department also runs the Center for Research on Biological Clocks (CRBC). Faculty in the CRBC study circadian clocks in a wide range of organisms, including Neurospora, Drosophila, Monarch butterfly, and mouse. The CRBC hosts seminar speakers from all over the world, a yearly meeting of the Texas Society for Circadian Biology and Medicine, and a weekly journal club. These events provide the opportunity to expand our knowledge, meet leaders in the field, and to present our research for feedback. Last but not the least, there are many shared facilities, and helpful faculty and staff.

Give us 5 adjectives that describe you as a scientist.

Responsible, critical thinking, persistent, detail-oriented, patient