The Emerging Role of Cryo-Electron Tomography (Cryo-ET) in Industry
Cryo-electron tomography (Cryo-ET) is drawing attention across pharma and biotech, but what can it deliver to support drug discovery research today — and what might it enable tomorrow?
In the second session of Clovertex’s Scientific Computing webinar series, two leading experts, Dimitry Tegunov, Ph.D. (Genentech) and Maryam Khoshouei, Ph.D. (Novartis Institutes for BioMedical Research), discussed the current and future role of Cryo-ET in biopharma.
The conversation picked up where the previous webinar on Cryo-EM single particle analysis (SPA) left off. During that webinar, panelists were frequently asked about tomography and its applications in real-world drug discovery.
While many experts acknowledged that Cryo-ET is not yet widely adopted across industry settings, the sheer volume of questions made it clear: curiosity about Cryo-ET is growing, fast.
Three Key Cryo-ET in Industry Takeaways
Limits for SBDD, Potential for Pharmacology & the Promise of AI
Don’t expect Cryo-ET to replace Cryo-EM SPA in structure-based drug design (SBDD)
While Cryo-ET is powerful for visualizing biological complexity in situ— inside intact cells or native-like environments— it’s unlikely to replace Cryo-EM SPA for the core pharma use case of SBDD. As Dimitry Tegunov noted, the kinds of high-resolution structures needed to support medicinal chemistry decisions are likely not attainable for most proteins using Cryo-ET.
“For most of the proteins that are interesting to pharma, Cryo-ET is probably not going to deliver a high-resolution structure inside the cell — and maybe never will.”
Even with advances in throughput and image processing, the technique struggles with low abundance of the targets common in drug discovery pipelines. Simply put, resolution and speed rule in biopharma — and Cryo-ET can’t yet deliver on either at scale.
Cryo-ET's value may lie in pharmacology rather than structural biology
Instead of SBDD, the real opportunity for Cryo-ET in industry may be understanding the functional effects of compounds at the cellular level. Panelists emphasized that pharmacologists — rather than structural biologists — may benefit most from Cryo-ET's ability to observe ultrastructural changes in organelles and tissues before and after treatment.
“If we treat organelles or tissues with a compound and can see what changes — even without atomic resolution — that's where Cryo-ET could be very useful.”
This shift in focus could broaden Cryo-ET’s audience within drug discovery teams, positioning it as a complementary technique for exploring cellular responses, mechanisms of action, or compound profiling.
The Holy Grail? AI for detecting subtle changes in tomograms
Interpreting ultrastructural changes in tomograms is extremely challenging for human researchers — the signal is sparse, and the noise is high. Tegunov emphasized that AI could play a transformative role in revealing patterns or phenotypes that aren't obvious to humans.
The vision: feeding large volumes of tomographic data into machine learning systems that can identify changes, generate hypotheses, and ultimately be used as powerful pillars supporting omics-scale biological modeling.
Cryo-ET Challenges and Enablers
“I’m more optimistic about Cryo-ET’s role in understanding cellular complexity than in solving high-resolution structures. AI may eventually uncover changes we can’t see with human eyes.”
Despite the promise, both panelists were candid about the limitations of Cryo-ET that have so far limited broader adoption in fast-paced biopharma drug discovery settings:
- Resolution and throughput are critical bottlenecks
- Sample preparation is complex, and the learning curve is steep
- Use cases must intersect technical feasibility and pharma relevance
To make Cryo-ET more accessible to industry teams, panelists emphasized the role of infrastructure — especially scalable compute environments, workflow automation and new software tools.
Cloud-based solutions, GPU-accelerated processing, and standardized pipelines can all help reduce friction and bring Cryo-ET closer to practical use in drug discovery. Tegunov also shared progress on Relay, a web-based platform he is developing, that could streamline Cryo-ET pipelines for broader accessibility.
Looking Ahead: The future for Cryo-ET in Biopharma R&D
Cryo-ET is not yet “fully ready for prime time” in drug discovery — at least not in the same way SPA has been embraced. But its future could be bright in compound profiling, cellular imaging, and AI-assisted systems biology.
As the field matures, strategic collaborations between academia and industry — like those between Novartis and the Friedrich Miescher Institute — will be key to pushing Cryo-ET toward broader utility in biopharma.
“Cryo-ET isn’t mature enough for drug discovery yet — but I’m optimistic. It can still help us answer key biological questions in the future.”
Stay tuned for future webinars in the Clovertex series and watch the full Cryo-ET session above to hear firsthand from experts who are exploring this potentially transformative frontier in industry.
Have questions or want to learn more?
Contact Clovertex for more information on Cryo-ET and how it could impact your drug discovery research.
