Finding inspiration in drug development from the laws of nature

Applying the lessons of evolution to drug development can lead to dramatic insights. Like clothes made from the flax plant, Dr. Bryan Dickinson reassembles biological building blocks from nature into new proteins with therapeutic potential. One example is an RNA-targeting technology for genetic therapy, what Dickinson likens to a “humanized” CRISPR-Cas system. View Halo Profile >>

Tell me about your research…

Our laboratory employs synthetic organic chemistry, molecular evolution, and protein design to develop molecular technologies to study chemistry in living systems. Our current primary research interests include – how chemical modifications to cysteine residues are controlled and regulate cell signaling; developing new biosensing and synthetic biology strategies to reprogram and control biomolecular interactions; and developing synthetic biology-based tools to interrogate and exploit epitranscriptomic regulation. Our guiding principle is that our ability as chemists to create functional molecules through both rational and evolutionary approaches will lead to new breakthroughs in biology and medicine.

Our guiding principle is that our ability as chemists to create functional molecules through both rational and evolutionary approaches will lead to new breakthroughs in biology and medicine.

Can you explain that to a non-scientist?

We are motivated by the idea that engineered biological systems can provide solutions to seemingly intractable problems in biology and medicine. We find biological “parts” from nature and repurpose them for our own needs in basic research or even therapeutic development.

We are motivated by the idea that engineered biological systems can provide solutions to seemingly intractable problems in biology and medicine.

To repurpose them for our own needs, sometimes we can use our intuition to figure out how to assemble the parts together to create the new things we need. Sometimes, however, the target function is too complex – and beyond our understanding. In this case, we use evolution – nature’s design principle – to endow molecules with function. This research strategy – molecule creation to application – provides a feedback loop between design, testing, and application, allowing us to better understand how to interact with and control biological systems.

This research strategy – molecule creation to application – provides a feedback loop between design, testing, and application, allowing us to better understand how to interact with and control biological systems.

How could it someday impact patient lives?

Much of our research is rather basic – understanding the processes that drive disease – and is therefore quite removed from translation. However, sometimes our research is directly motivated by solving problems in medicine. For example, we recently developed a technology to interact with RNA, the “intermediate” in the central dogma that links the DNA blueprints to proteins that mediate health or disease.

The idea is that RNA-targeting genetic therapies offer advantages in terms of safety and clinical utility. Our system is in essence a “humanized” CRISPR-Cas system, opening up possibilities for developing these tools into therapies. Although still early stages, we are going to begin testing these and related tools in preclinical models to better understand the potential of our technologies. If successful, we would attempt to develop these approaches into clinical candidates – and test them in patients – in the relatively near future.

Our system is in essence a “humanized” CRISPR-Cas system, opening up possibilities for developing these tools into therapies.