From cancer cells to climate-resilient trees: how CRISPR is transforming research at VIB

A cancer cell escaping therapy. A yeast cell revealing the secrets of gene regulation. A poplar tree engineered without introducing foreign DNA. At first glance, these discoveries seem to have little in common. Yet they are all connected by the same revolutionary technology: CRISPR, or – big breath – Clustered Regularly Interspaced Short Palindromic Repeats. ​

Part of the antiviral defense system of many bacteria and archaea, CRISPR sequences are short stretches of DNA that store genetic fragments from viruses the microbes have encountered before. CRISPR allows bacteria and archaea to learn from past infections, like our own immune system does. When a familiar virus attacks, the CRISPR machinery recognizes its genetic signature and directs Cas (‘CRISPR-associated’) proteins to cut the invader's DNA, stopping the infection in its tiny tracks.

Just over a decade ago, scientists adapted this natural defense mechanism into one of the most powerful tools in modern biology. What began as a way to precisely edit DNA has since evolved into something much bigger. Today, CRISPR is helping researchers uncover how genes work, understand the mechanisms behind disease, engineer more sustainable crops, and accelerate the search for new treatments.

At VIB, scientists are applying CRISPR in remarkably diverse ways. Some are developing the next generation of genome-editing tools, making it easier to introduce precise changes in plant genomes. Others develop large-scale CRISPR screening and precision-editing approaches to uncover how genes and genetic variants shape biological function, revealing the molecular processes that underpin life. In cancer biology, researchers are harnessing CRISPR screening to uncover the genetic regulators that allow tumors to adapt and become resistant to therapy. And genome editing is opening new possibilities for creating crops and trees that are better equipped to meet the challenges of a changing climate.

Building better molecular tools

CRISPR has transformed biological research, but the technology is far from finished. Scientists continue to develop new genome-editing tools that are more precise, more efficient, and capable of tackling increasingly complex biological questions.

At the VIB-UGent Center for Plant Systems Biology, Thomas Jacobs and his team are helping drive that progress. ​

“Our goal is not just to apply existing genome-editing technologies to a single research challenge,” says Thomas. “We focus on improving the tools themselves, making CRISPR more powerful and accessible for researchers working across plant science.”

One challenge is that not all CRISPR systems perform equally well. While newer approaches such as base editing allow scientists to change individual DNA letters without cutting the famous double helix, their efficiency can vary dramatically depending on the target and the system being used. To address this, the Jacobs lab developed ITER (Iterative Testing of Editing Reagents), a high-throughput platform that enables researchers to rapidly test and optimize genome-editing components. ITER allows hundreds of potential editor designs to be evaluated in parallel, which accelerates the development of improved genome-editing tools.

Using ITER, the team identified and refined new base-editing systems for crops such as wheat and maize. The result was a substantial increase in editing efficiency, demonstrating how systematic testing can unlock the full potential of emerging CRISPR technologies.

The lab has continued to build on these advances, for example by developing improved strategies for large-scale genome editing, making it easier to generate multiple mutations simultaneously. These advances make large-scale genetic studies faster, more practical, and more affordable.

Scale is what brings us to our next stop on VIB’s CRISPR tour.

Understanding genetic variation, at scale

For decades, biologists have studied genetic changes one at a time. Alter a gene, observe the result, and gradually build a picture of how living cells work. It is a powerful but slow approach. After all, genomes contain thousands of genes and vastly more possible variants, many of which interact in complex and often unexpected ways. ​

So... what if researchers could investigate thousands of precisely defined genetic changes simultaneously?

At the VIB-KU Leuven Center for Microbiology, Sibylle Vonesch and her team develop CRISPR technologies that make this possible in microorganisms. Their work spans both familiar model organisms such as yeast and E. coli as well as less conventional microbes, with the goal of enabling large-scale genetic experiments across a much wider range of biological systems. Their toolkit includes ways to switch genes on or off, but a particular focus is high-throughput precision editing. This allows the team to move beyond asking what a gene does and systematically test how specific DNA-letter or amino-acid changes affect biological function, and increasingly, how those variants interact in combination.

By coupling these perturbations to DNA barcodes, the team can construct large libraries of genetic variants, study them together in a single experiment, and determine how individual changes affect cellular traits or molecular processes. ​

But building the technology is only part of the story. The lab uses these tools to explore how changes in DNA translates into changes in biology. How can a seemingly small change in a codon alter a protein's activity or expression? Which parts of a biological molecule are particularly sensitive to mutation? And why can the same mutation have very different effects depending on the other variants present in a cell?

“What excites me is that we can now move beyond studying mutations one by one,” says Sibylle. “Even changes that leave the protein sequence unchanged, such as synonymous mutations, can have important biological effects. By testing thousands of variants, and increasingly combinations of variants, we can move beyond individual examples and start to uncover general principles: which changes matter, and why.”

Together, these approaches turn CRISPR into more than a tool for changing genomes. They make it possible to systematically link DNA sequence to molecular function and, ultimately, to phenotype. This can help researchers make sense of the thousands of variants found in genomes, and provide principles for engineering better industrial microbes or designing new biological systems.

And those insights can have applications far beyond microorganisms. Better trees, for example.

Rewriting nature's raw materials

When people think about CRISPR, they often think about medicine. Yet some of its most transformative applications may be found in the plants that provide our food, materials, and renewable resources.

At the VIB-UGent Center for Plant Systems Biology, Wout Boerjan and his team are exploring how genome editing can help create a more sustainable bioeconomy. Their research focuses on plant biomass, the renewable raw material used to produce everything from paper and textiles to biofuels and biochemicals.

A key area of interest is lignin, the complex molecule that gives plants their strength and structure. While lignin is essential for plant growth, it can also make biomass more difficult to process. By understanding the genes that control lignin production and composition, Boerjan's team aims to develop plants that are easier to convert into sustainable materials and renewable products. CRISPR provides an important tool to achieve that goal. ​

Recently, the researchers demonstrated the potential of this approach in poplar trees. Even more, they introduced targeted genetic changes without leaving foreign DNA behind. The genome-editing machinery performed its task and then disappeared, resulting in trees that contained only the intended genetic modifications. No leftovers. ​

“Beyond improving our understanding of plant biology,” says Wout, “genome editing is helping researchers develop practical solutions for a world facing climate change, resource scarcity, and growing demand for sustainable materials.”

By revealing how plant genomes shape biomass production and enabling increasingly precise genetic improvements, the technology is opening new opportunities to build a greener and more sustainable future.

Medicine is, of course, another field where CRISPR can have a big impact. ​

Finding cancer's escape routes

One of the biggest challenges in cancer treatment is that tumors evolve. A therapy may initially work well, only for cancer cells to adapt, survive, and eventually become resistant.

At the VIB-KU Leuven Center for Cancer Biology, Olaf Klingbeil and his team are investigating the gene regulatory networks that drive this process. Their goal is to understand how cancer cells change their identity in response to treatment and find the regulators that enable them to escape therapy.

To do this, the lab uses CRISPR-based functional genomics. Returning to a previous theme, rather than studying genes one at a time, the researchers screen large sets of chromatin regulators, transcription factors, and signaling components to determine which ones influence tumor progression and treatment response.

"The power of this approach is that we can do it in the right context,” says Olaf. “We use patient-derived organoids and tumors in mice. Combining CRISPR screening with single-cell sequencing and DNA barcoding lets us track how tumor cells adapt during therapy and pinpoint the genes that drive those changes."

If researchers can identify the molecular mechanisms that allow cancer cells to switch states and develop resistance, they may be able to prevent those transitions before they occur or reverse them once they have begun. In other words, by revealing cancer's escape routes, CRISPR is bringing us closer to more durable and effective treatments.

A technology changing how we do science

How can we build better genome-editing tools? How do genes shape biological function? How can we create more sustainable plants and materials? Why do cancers become resistant to treatment?

At VIB, researchers are using CRISPR to help answer all of these questions.

That diversity is perhaps the technology's greatest strength. Originally developed as a tool for genome editing, CRISPR has evolved into a powerful platform for discovery. ​

For Thomas Jacobs, CRISPR is a technology to be refined and expanded. For Sibylle Vonesch, it is a way to connect genetic variation to biological function. For Wout Boerjan, it offers new opportunities to build a more sustainable bioeconomy. And for Olaf Klingbeil, it provides a powerful approach to understand how cancers adapt and resist treatment.

As CRISPR continues to evolve, so will the possibilities it creates. Across VIB, researchers are pushing the boundaries of what this technology can do, turning a bacterial defense mechanism into a driver of discovery, innovation, and impact. From plants and microbes to cancer and complex genetic networks, CRISPR is helping shape the future of life sciences, one breakthrough at a time.

Gunnar De Winter

Science Communication Manager, VIB

• gunnar.dewinter@vib.be