Postdoc Appreciation Week Spotlight: Guoming Gao

September 21-25, 2026, 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, we're hearing an update from Guoming Gao, California Institute of Technology, originally spotlighted in 2025.  Click here to read his first spotlight.

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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. Single-molecule biophysics is a powerful tool to characterize molecular features and dissect mechanisms such as interaction dynamics, stoichiometry, and kinetics. Yet, it relies on proper context to reveal true biological insights. Quantitative functional genomics uses sequencing to measure protein binding to DNA/RNA, modifications on them, and the gene expression profile as an outcome. Therefore, functional genomics pairs well with single-molecule biophysics: the former provides rich context to aid interpretation of the latter's data and clarify their biological relevance, while the latter provides direct proof of mechanism and event-to-event heterogeneity to elucidate global trends found by the former. That's why I joined the Mitch Guttman lab here at Caltech to continue my journey in RNA biology by combining my PhD toolbox of single-molecule biophysics with this lab's expertise in quantitative functional genomics.

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 quantitative functional genomics.

For ncRNA function, my main motivation stems from the so-called “dark transcriptome paradox”: namely, why do cells need 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.

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 my realizing it, so I sometimes have to time myself carefully to ensure experiments still get done.

The most striking update to my answer this year is that I've learned how important it is to preserve your own reading and thinking time. Personal growth as a scientist can only take place when you learn and think deeply. What is the current status of the field based on the most recent papers and preprints? What are the core questions of the field that most researchers would get excited about? What are the fundamental principles behind algorithms or common practices (in both experiments and data processing)? Why have they taken this form as a community consensus has developed over time? These are all very important questions that help shape your own tastes as a scientist. Meeting with colleagues is great, but ultimately answering these questions requires reading and deep thinking by oneself. Time can easily slip away each day, so it's critical to learn how to preserve dedicated time for deep thinking.

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” and to guide the formation of distinct molecular assemblies. We hypothesize that local transcription events, and thus the presence of either ncRNA or an intron in a nascent protein-coding transcript, might provide such context. I’m working on multiple scenarios and mechanisms that function under this paradigm.

If confirmed, 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? 

The most exciting moment so far was seeing a hypothesized RNA-guided protein assembly being reproduced not only by different methods of super-resolution imaging (both localization-based and fluctuation-based) but also across single-molecule imaging and genomics, with a specific expression profile change. This reflects exactly why I want to live my scientific life at the interface of the two fields.

Personal Touch 

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

I think I only learned this very recently when my projects ran into some major bottlenecks. My best friend came to visit me, and we did a road trip north from Los Angeles to San Francisco. The beautiful views of the Big Sur shoreline along the way really refreshed me. I even squeezed a twin mattress into my car so that I could just park by the sea and enjoy the sea, the wind, and the sunshine while in bed. It's simply amazing but also coincidental that we found some ways to get around those bottlenecks right after this relaxing trip. That's really an aha moment for me: it's actually not that you need to work hard to get that work-life balance, but instead that you need to live your life and relax well to sustain your work. Rest up. Don't get drained.

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

Eating, swimming, and going to the gym. Anything that is on a regular, periodic schedule helps a lot with 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 from either a readout or some discussions with others. Having something on a regular schedule (for me, last year it was going to the gym twice a week, mostly on Tuesdays and Saturdays) is extremely helpful for maintaining your rhythm of life.

One update this year is that I've started a new gym schedule! I now do 3 training sessions and do cardio on 2 other days per week. It's been working so well, and I'm now in better shape. I feel proud of myself : )

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 involve 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 avenues originating from a few dots. The degree of freedom is absolutely much higher than when writing a research paper, which was something I wasn’t used to at first. Writing a good grant is 1000% a learned skill. I highly recommend the guidelines for grant writing from our neighboring lab, the Elowitz lab: https://www.elowitz.caltech.edu/teaching, specifically the section at the bottom of the page named “Advice: ‘10’ Commandments for Writing Grants and Fellowships”. This is super honest and practical advice that I found extremely useful. 

For this year, the funding situation has been extremely difficult these days. Just hang in there and don't lose faith in yourself! One useful trick is to learn from how industry people handle layoffs and rejections in job searches. They have a lot of great articles on the right mindset for handling these situations, which have been really helpful to me. There are simply a thousand reasons behind a rejection, and thus one should definitely not overthink it. 

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.