Science
My PhD research is pretty far removed from most people’s everyday experience. It’s technical, specialized, and not the kind of science that naturally grabs a general audience. Because of that, I’ve spent a lot of time learning how to turn my research into a story that makes sense to people who have no training in biochemistry.
Along the way, that effort has paid off. I’ve won Best Presentation Awards at both UVic’s graduate research symposium for a general audience and my department’s biochemistry and microbiology symposium, and I’ve had students from completely different fields tell me they understood my entire talk, even though the science wasn’t anywhere close to their own research. Making complex science feel clear, engaging, and approachable is now a core part of how I think about both my research and my science communication work.
In the lab, my work is driven by curiosity about the enzymes that control how our body’s cells behave, and what happens when those enzymes become mutated and dysregulated.
I study lipid signaling enzymes, the molecular switches that help regulate powerful cellular processes, using a toolkit that spans structural biology, biochemistry, and mass spectrometry. By mapping how these enzymes function at the molecular level, my research aims to shed light on the mechanisms underlying disease and, ultimately, how they might be targeted therapeutically.
The sections below offer a closer look at the questions I ask, the tools I use to answer them, and the support that makes this work possible.
PI3Kα
If you know someone who has had cancer, there’s a good chance the enzyme PI3Kα played a role in their disease. Mutations in this enzyme are among the most common drivers of human cancers.
PI3Kα produces a lipid called PIP₃, which functions like a cellular switchboard—activating signaling pathways that tell cells when to grow and divide. When mutations cause PI3Kα to become stuck in the “on” position, these growth signals spiral out of control, leading to unchecked cell proliferation (i.e. cancer).
Much of my research focuses on the part of PI3Kα that acts as the enzyme’s brake, known as the regulatory subunit. PI3Kα can pair with one of five different regulatory subunits, and I study how these different combinations affect the enzyme’s behaviour. I also investigate what happens when cancer-associated mutations occur in this regulatory “brake,” rather than in the catalytic “engine” of the enzyme, which has already been studied extensively.
By better understanding how PI3Kα is regulated, and how that regulation fails in disease, we can design more effective, more selective therapies for cancer patients.
PIKfyve
PIKfyve is the only enzyme in the human body that produces a lipid called PI(3,5)P₂, which is essential for keeping a cell’s internal “garbage sorting” system running smoothly. When PIKfyve doesn’t work properly, this waste-management system breaks down; cellular trash accumulates until the cell ultimately dies.
Because of this central role, PIKfyve has become a major target for therapeutic development. Drugs that inhibit this enzyme are currently in clinical trials for a range of conditions, including cancer and neurodegenerative diseases such as ALS. My research focuses on uncovering the molecular mechanisms that govern how PIKfyve works, with the goal of informing the design of more precise and effective therapies for people affected by these diseases.
HDX-MS
One of the most powerful tools my lab uses to study protein structure is HDX-MS (hydrogen-deuterium exchange mass spectrometry). At its core, this technique takes advantage of the incredible sensitivity of mass spectrometry, which can detect extremely small changes in molecular weight.
HDX-MS works because certain hydrogen atoms in a protein can be swapped for deuterium, a heavier form of hydrogen. Parts of a protein that are loose or flexible exchange hydrogen for deuterium very quickly. In contrast, regions that are tightly folded or protected exchange much more slowly.
By briefly soaking proteins in “heavy water” and measuring these changes with a mass spectrometer, we can see how a protein’s shape shifts when it becomes active, or pinpoint where other molecules, such as antibodies or drug candidates, bind. This makes HDX-MS a powerful way to connect protein structure with function.
X-Ray Crystallography
If you’ve ever left a glass of salty water out on the counter and come back to find salt crystals, you’ve already seen crystallization in action. Under the right conditions, proteins can form crystals too. X-ray crystallography is a technique that uses these crystals to determine the three-dimensional structure of a protein, essentially taking an atomic-scale picture.
To do this, I grow crystals of a purified protein and send them to a particle accelerator, where beams of X-rays are shot through the crystal. As the X-rays interact with the atoms inside, they scatter and produce a distinctive pattern of spots called a diffraction pattern. Powerful computer algorithms then analyze this pattern to reconstruct the protein’s 3D structure, revealing how it is shaped and how it works at the atomic level.
Barlow-Busch I, Walsh EE, Nyvall HG, Burke JE. Activity and dynamics of p110α are not differentially modulated by regulatory subunit isoforms. Adv Biol Regul. 2025 Nov 4:101128.
Shaw AL, Barlow-Busch I, Burke JE. Molecular basis for regulation of the class I phosphoinositide 3-kinases (PI3Ks), and their targeting in human disease. Biochim Biophys Acta Mol Cell Biol Lipids. 2025 Dec;1870(8):159689.
Pemberton JG, Barlow-Busch I, Jenkins ML, Parson MAH, Sarnyai F, Bektas SN, Kim YJ, Heuser JE, Burke JE, Balla T. An advanced toolset to manipulate and monitor subcellular phosphatidylinositol 3,5-bisphosphate. J Cell Biol. 2025 Jun 2;224(6):e202408158.
Bissegger L, Constantin TA, Keles E, Raguž L, Barlow-Busch I, Orbegozo C, Schaefer T, Borlandelli V, Bohnacker T, Sriramaratnam R, Schäfer A, Gstaiger M, Burke JE, Borsari C, Wymann MP. Rapid, potent, and persistent covalent chemical probes to deconvolute PI3Kα signaling. Chem Sci. 2024 Nov 12;15(48):20274-20291.
Barlow-Busch I, Shaw AL, Burke JE. PI4KA and PIKfyve: Essential phosphoinositide signaling enzymes involved in myriad human diseases. Curr Opin Cell Biol. 2023 Aug;83:102207.
University of Victoria
| Date | Award | Funding |
| 2024/5 – 2027/5 | Canada Graduate Scholarship – Doctoral (NSERC) | $120,000 |
| 2022, 2024, 2025, 2026 | President’s Research Scholarship | $20,000 |
| 2022/9 – 2023/8 | Canada Graduate Scholarships – Master’s Program (NSERC) | $17,500 |
| 2022/07 | University of Victoria Graduate Entrance Award | $5,000 |
Total: $162,500
University of Guelph
| Date | Award | Funding |
| 2021/6 | Mac Lewis Memorial Classics Travel Grant | $3,000 |
| 2021/6 | Faculty Prize in Classics | $100 |
| 2021/4 | Dr. R.A.B. Keates Biochemistry Scholarship | $1,000 |
| 2021/4 | Chemical Institute of Canada Prize Silver Medal in Biochemistry | n/a |
| 2021/4 | Dr. Frances Sharom Biochemistry Scholarship | $1,000 |
| 2020/4 | Analytical Biochemistry Scholarship | $500 |
| 2020/4 | Honour’s Biochemistry Scholarship | $500 |
| 2019/10 | Dean’s Scholarship | $2,000 |
| 2017/9 | University of Guelph Entrance Scholarship | $3,000 |
Total: $10,600
Isobel Barlow-Busch 