Proteins are functionally diverse biomolecules with a vast range of potential applications. From catalyzing complex industrial reactions under mild conditions to enabling life-altering medical devices such as glucose monitors for diabetics, these biological nanomachines have already transformed modern society. Synthetic biology aims to further expand the capabilities of our biotechnological toolbox by applying engineering principles to redesign natural systems, including proteins. Molecular information on the systems we are engineering is critical to guide this process, and modern synthetic biology depends on decades of structural biology that has guided our understanding of protein structure and function. However, this information focuses strongly on proteins in a liquid medium, and comparatively little is known about how proteins interact with solids. This knowledge gap restricts what we can do with these useful molecules since solid materials are just as prevalent as liquids in our everyday lives.
Our research program aims to start filling in these holes using whatever tools we can find, make, or dream up. Only a handful of biochemical tools are currently used to study enzymes at solid interfaces, such as surface plasmon resonance (SPR), isothermal titration calorimetry (ITC), computational modelling, and enzymatic activity assays. On top of using these we will also be designing our own tools and methodologies to infer protein properties at solid surfaces. With so much of the landscape uncharted, we’ll be pioneers of sorts, but that’s the exciting part! Functional proteins have incredible potential in medical, industrial, and environmental science, and solid interfaces are everywhere. Why stay limited only to liquid media? Ultimately, the more we learn in this space, the more we’ll be able to make use of our knowledge to create biotechnological tools with real world applications. And the more tools we create, the more we can learn from them. Progress begets progress, and I for one am excited to see just what we’ll be able to bring to life.
Upcoming Projects:
Here are some project ideas just waiting for the right person to pick them up! See yourself working on one or more of these projects with our group? Then check out our opportunities or send me a message!
Engineering enzymatic plastic degradation and affinity
Plastics are widely used in modern society, but due to their resilience towards both chemical and biochemical degradation processes, they are remarkably persistent in the environment. Waste migration patterns lead to their accumulation in waterways and ecosystems, and plastic pollution has become an increasing global concern. Recently, some of the big news in environmental biotech has focused on the discovery of plastic degrading enzymes. Unfortunately, they’re not all that efficient yet, and we don’t understand them well enough to really fix those issues. We aim to change that using high-throughput affinity screening, mutational scanning, and the biophysical characterization tools that work with solids.
Training computational algorithms that predict protein-solid interactions
Computational protein design tools can significantly assist protein engineering efforts by predicting the effects of mutations on protein stability or function. However, they are generally poorly suited to handle scenarios involving protein-solid interactions, as they are by and large the result of characterizing protein structures in solution. During our other projects, we will be generating large datasets correlating protein sequence to solid-binding or -modifying properties. Rather than discard this information-rich data, we will use machine learning to parse through it with the goal of developing protein engineering tools capable of handling protein-solid interactions.
Improving electrochemical cofactor regeneration processes
Enzymes are incredibly relevant to sustainable industry, as they can substantially improve the energy efficiency of industrial processes. Many industrial enzymes that are already in use today are from the redox enzyme family, which depend on expensive cofactors to function. To improve the efficiency of these redox enzyme processes, we will develop a system to regenerate these cofactors using an electrical potential. Along the way, the needs of this system will have us delving into the dynamics of enzyme-scaffold interactions, including enzyme loading, diffusion rates, scaffold material properties, and geometry effects.
Developing self-cleaving biomimetic hydrogels
Biologically-compatible materials are incredibly important medical technology tools that enable treatment options for a wide range of diseases. Biomimetic hydrogels are a subset of these useful materials with uses that include the targeted administration of therapeutics to a desired site. Currently, simple diffusion is used to release these agents from the hydrogels, which limits the accessible dosages that can be achieved. In this project, we will expand upon existing biomimetic hydrogel technology to create a protein-linked hydrogel that can be degraded at will through the administration of a small molecule drug or in response to a biological marker.
Designing a continuous-mode insulin biosensor
Diabetes is a potentially crippling chronic illness characterized by dysregulation of blood sugar levels that affects hundreds of millions of people worldwide. If improperly managed, diabetes can lead to serious damage to organs and premature death. While diabetes management practices that monitor blood sugar levels in real time have significantly improved the quality of life of people living with diabetes, these aren’t perfect. One missing piece of the puzzle is the lack of technology to easily measure insulin levels. To address this, we will adapt an engineered insulin receptor to the design of a continuous insulin sensor. This project will use a computationally-guided approach to study how tethering constrains protein motion at a solid surface.
Your project idea here!
If you have an idea for a project that you are keen on pursuing and think that this is the laboratory for it, we’re always open to new ideas and suggestions!