Brian Kuhlman
Eddie Goldenberg Distinguished Research Chair of Canada in Computational Protein Design
Dr. Brian Kuhlman is internationally recognized as a leading authority in computational protein design — the use of computer modelling to create proteins with specific properties and functions.
His work has been instrumental in transforming the field from a largely theoretical idea into an established scientific discipline capable of designing proteins with new sequences, structures and functions.
What is the main challenge your Eddie Goldenberg Research Chair of Canada program is addressing, and how are you approaching it?
Proteins are the molecular machines of life, and the ability to design them from scratch is transforming medicine, diagnostics and biotechnology. Recent breakthroughs in AI — from AlphaFold's structure predictions to neural networks that optimize protein sequences — have made it possible to create proteins with predefined shapes and interactions. The central challenge now is translating these computational capabilities into proteins that perform useful functions in the real world.
My research program at UBC will address this challenge on two fronts: applying computational protein design to create new therapeutics and diagnostics, including a next-generation dengue vaccine, tumour-selective cancer drugs, and protein-based biosensors; and developing the AI tools needed to design proteins that change shape in response to their environment. These capabilities will be shared with collaborating laboratories and industry partners across BC and Canada.
What is the main thing you would like to achieve as an Eddie Goldenberg Research Chair of Canada, and what are the potential impacts of your work?
My laboratory aims to (1) develop and share new computational methods for protein design, (2) apply these methods towards fundamental problems in protein design, and (3) create proteins with valuable applications in medicine, research and industry.
While recent advances in AI-based structure prediction and sequence optimization have transformed the field of protein design, major challenges remain. These include designing antibodies with precisely tailored binding loops, engineering enzymes that catalyze novel chemical reactions, and creating proteins that change their behaviour in response to specific environmental cues, such as the acidic microenvironment of a tumour. To solve these problems, my laboratory will develop new AI-based tools for designing enzyme active sites and building proteins with programmable conformational switches. These methods will be released openly and will allow laboratories worldwide to create more effective protein-based therapeutics and enzymes that contribute to a more sustainable economy.
Specific goals include: a universally safe dengue vaccine (dengue infects hundreds of millions of people annually and no fully safe vaccine currently exists) based on designed protein assemblies that mimic the virus surface and elicit broad protective immunity; tumour-selective cancer therapeutics that activate only in the acidic microenvironment of tumours, reducing off-target toxicity; and biosensors that enable real-time monitoring of peptide hormones such as insulin, with applications in diagnostics and personalized medicine.
The broader impact of this work extends beyond any individual application. New computational tools will be released open-source, making them freely accessible to researchers worldwide. We will also translate these methods into collaborative projects with UBC researchers and B.C. industry partners, and the program will train a new generation of scientists at the intersection of AI and protein engineering — a skill set in high demand across academia and the global biotechnology sector.
What is your primary motivation behind the research you do? What drew you to this work?
Each protein in your body adopts a unique and beautiful shape that promotes specific interactions with other molecules in your body. It is these fantastic shapes and structures that first drew to me to protein design. I wanted to be able to create new shapes that have not been seen before in nature. Growing up I loved Legos, designing proteins feels like a very similar endeavor except that with protein design we hope that we can create molecules that benefit human health.
What drew you to UBC to do this work, and what are you most looking forward to about coming here?
By its nature, protein design is a highly collaborative area of science. We make use of methods and concepts developed by computer scientists, physicists and chemists while aiming to create molecules that can be used by biologists and physicians. UBC has strong expertise in all these areas and a track record of promoting collaborations between different groups on campus.
What does it mean to you to have been appointed as an Eddie Goldenberg Research Chair of Canada, and how is it going to help you advance your already internationally recognized research?
This research chair will provide the stability and freedom to tackle fundamental problems in protein design while at the same time allowing us to advance the discovery of designed proteins that have important applications in medicine, research and industry.
