September 15-19, 2025, is National Postdoc Appreciation Week. Since 2009, the National Postdoctoral Association (NPA) has sponsored this annual celebration to recognize the significant contributions that postdoctoral scholars make to research and scientific discovery. Check out the NPA website to view the virtual and in-person events being held this week. 

This week, BPS will be highlighting postdoc members on the blog. Today, read about Guoming Gao, California Institute of Technology.

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Background & Inspiration 

1. Can you tell us a little about your background and what brought you to your current postdoc position? 

I was trained as a single-molecule biophysicist and became an RNA enthusiast in the Nils Walter lab at the University of Michigan–Ann Arbor. Being able to directly see biomolecules in action—one molecule at a time—and uncover the “life story” of each has always motivated me to pursue a career at the interface of physics and biology. 

Throughout my PhD projects, I realized that single-molecule biophysics is a powerful tool to dissect mechanisms such as interaction dynamics, stoichiometry, and kinetics, but only if the target molecule is clearly defined. For example, if you observe an interesting biological phenomenon but lack genetic or biochemical clues about which biomolecules are responsible, single-molecule biophysics alone can be somewhat blind, and its low throughput nature makes it difficult to profile molecules on the omics scale. 

I decided to expand my toolkit into higher-throughput omics approaches to better complement my use of single-molecule tools for RNA biology questions in my future lab. The Mitchell Guttman lab at Caltech turned out to be the perfect fit for three main reasons. First, the SPRITE technologies developed there are among the few omics-scale profiling methods that measure intermolecular distances and interactions within cells—exactly what single-molecule biophysics also measures. This creates an orthogonal pair of approaches where my skills and the lab’s assets strongly complement each other. SPRITE also holds great potential to capture interactions among proteins, RNAs, and DNA across nanometer to micrometer scales, covering essentially the entire spectrum of molecular biology inside the cell. Second, lncRNA function—the question I’m most passionate about—is a research focus in the Guttman lab, particularly through its historical work on Xist. Third, both Mitch and I strongly believe in fusing imaging/biophysics with genomics, and we share the conviction that this integration of mindsets and tools could transform research in RNA biology. 

2. What inspired you to pursue research in your field? 

I pursue research in two fields: non-coding RNA (ncRNA) function, and single-molecule biophysics (aided by integration with omics, as described above). 

For ncRNA function, my main motivation stems from the so-called “dark transcriptome paradox”—in other words, what is the function of the widespread transcription of RNAs that neither code for proteins nor even leave the nucleus? This paradox fascinates me because many of these ncRNAs are highly expressed and interact with essential proteins, despite showing little sequence or structural conservation. 

On the single-molecule side, my motivation is the search for direct evidence of cellular processes. Much of molecular biology is built on indirect evidence. But for example: if a molecule is thought to translocate sequentially, what could be more direct than actually seeing a single molecule dwell in one subcellular region before moving to another? If molecules are thought to interact, what could be more direct than observing two molecules co-diffuse over time inside a living cell? These beliefs are what shape my dedication to both fields. 

Daily Work & Routine 

3. What does a typical day look like for you as a postdoc? 

I manage my experiments as projects and timelines using Notion, so I usually start my day by reviewing my plans there and making adjustments as needed. Since we work with mouse embryonic stem cells (mESCs) to study the ncRNA Xist, my next step is usually feeding the cells with medium containing differentiation inhibitors. 

The rest of my day involves carrying out the experiments, recording results, and planning next steps. Along the way, I often discuss projects with labmates, exchanging ideas and helping each other interpret results. I typically do imaging at night since my single-molecule imaging runs for 4–5 hours, and I want to leave daytime hours free for other users at our shared facility. Meetings—whether lab meetings, collaborations, or seminars on campus—are also part of the routine. 

4. Do you have a favorite part of your daily routine—or a task you look forward to most? 

Definitely imaging. I love watching the molecules in action during live-cell imaging. Even for fixed-cell imaging, seeing the picture emerge in front of me and using my understanding of microscopy to tune parameters so the molecular events of interest are revealed brings me more joy than all other activities of the day combined. 

5. What’s one part of your day that people might find surprising or unexpected? 

How much time gets spent in discussions. I often have great conversations when colleagues seek input on hypotheses or data analysis strategies. It’s just surprising how quickly the day can slip away in meetings without realizing it, so I sometimes have to time myself carefully to ensure experiments still get done. 

Research & Impact 

6. Can you briefly describe your research project and why it matters? 

My research projects are centered around RNA-guided, localized mechanisms for gene regulation. The expression of specific sets of genes is precisely regulated during both physiological and pathological processes. Yet, it remains unclear how the same set of regulatory machinery can be guided to some genes but not others, especially when the genes or regulatory DNA elements share sequence similarities. Therefore, localized mechanisms are needed to distinguish one gene from another by providing some “context.” We hypothesize that local transcription events, and thus the presence of either ncRNA or the non-coding part (intron) of a coding mRNA, might provide such context. I’m working on multiple scenarios and mechanisms that function under this paradigm. 

If tested to be true, these exemplary cases would consolidate this alternative paradigm and advance our understanding of gene regulation, contrasting with the traditional view governed by transcription factor (TF)–DNA interactions. Proteins such as TFs are made in the cytoplasm, and they intrinsically lack the localization information that nascent RNAs have, causing them to rely on the search process and the specificity of their DNA-binding domains (DBDs). Recent studies have shown theoretical and experimental limitations in both the search process and DBD specificity for explaining gene regulation. The RNA-guided localized mechanisms I’m working on could fill the gap where the traditional TF–DNA model fails.

7. What’s the most exciting discovery or moment you’ve had during your postdoc so far? 

I only started earlier this year, but so far, the most exciting moment was during single-molecule localization microscopy (SMLM), when I observed an RNA-binding protein degrader being recruited and clustering at a transcriptional bursting event marked by intron smFISH. Seeing such a mechanism play out directly at single-molecule resolution was pure joy—and it’s exactly why I want to dedicate my life to science. 

Personal Touch 

8. How do you balance life in the lab with life outside of it? 

I’m still adjusting to postdoc life, and I admit I’m still working on achieving balance—especially because I’ve been so energized by the science here. For me, the most important thing is to enjoy life in whatever form makes you happiest. Once you know the lifestyle you want, the path to it is very personal. I find that the great food and sunshine here in Pasadena help too. I love driving to nearby places to try signature dishes, which combines two of my passions: food and driving. 

9. What hobbies or activities help you recharge after work? 

Eating, swimming, and going to gym. Anything that is on a regular, periodic schedule help a lot on recharging since many experimental schedules are most often a bit chaotic, especially at the initial stages of establishing a protocol when you need to adjust here and there based on some real time feedback of either a readout or some discussions with others. Having something on a regular schedule (for me, it’s going to gym twice a week, mostly Tuesday and Saturday) is extremely helpful for securing your rhythm of life. 

10. Any fun lab quirks? 

Boba milk tea. It turns out our lab also has a lot of boba fans lol.

Advice & Future 

11. What advice would you give to someone just starting a postdoc? 

Start practicing grant writing as soon as possible. Although both are telling a story, writing a grant is very different from writing a paper. The main difference is that a paper is supported by solidly validated sets of data, where the story works to connect all the dots (evidence), while a grant is framed by rationale plus preliminary data, where the story serves to open up new revenues originating from a few dots. The degree of freedom is absolutely much higher than writing a research paper, which was what I didn’t get used to at first. Writing a good grant is 1000% a learned skill. I highly recommend our neighbor lab, Elowitz lab’s guidelines for grant writing: https://www.elowitz.caltech.edu/teaching, the section at the bottom of the page named “Advice: ‘10’ Commandments for Writing Grants and Fellowships”. They are super honest and practical advice that I found extremely useful.  

12. Where do you see yourself heading next in your career? 

I hope to lead my own research group at an academic institute in the future. I want to be at an institute like the University of Michigan, where researchers can do strong, creative work while maintaining a good pacing. Truly creative work can only be made by dedicated efforts towards questions that truly interest the researcher. Since those interests and tastes vary from one to another researcher, creative work should be unique and niche, rather than over-competitive, and thus should in principle have nothing to do with how fast it’s done. I see myself pursuing science in such an environment if the opportunity arises.