About This Project
Microplastics (MPs) are widely dispersed in nature and negatively impact the biosphere. Unlike larger plastic waste, MPs are too small to mechanically remove from the environment with nets or other methods. Protein-based plastic binding domains have the potential to efficiently detect and capture MPs from the environment. Since MP waste is extremely diverse (10 or more distinct types of MPs), we propose a yeast display engineering platform to establish diverse capture agents.
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What is the context of this research?
Microplastics (MPs) are small plastic particles that have been dispersed throughout the planet by human activities (MPs are defined here as any plastic between 1 nm and 10 mm in diameter). Millions of tons of MPs estimated to exist in nature. Unlike macroscopic plastics, MPs cannot be efficiently removed from the environments using nets or other established mechanical separation processes. In addition, there are easily 10 or more distinct types of MP contaminants, whose distribution, type, and amount varies dramatically as a function of environmental location.
What is the significance of this project?
Substantial research efforts are underway to engineer plastic-degrading enzymes, which can be used to digest MPs. However, the diversity and wide range of MP properties make it difficult to effectively deploy enzymes without concentrating MPs and identifying the type(s) of MP waste present in a sample. MPs are derived from 5 or more distinct plastics and can be modified physically, chemically, or biologically once dispersed in the environment. All of these challenges motivate the need to engineer plastic binding domains capable of capturing MPs with diverse properties. Such binding domains would facilitate identification of the presence of microplastics in a sample and capture and sequestration of the microplastics to facilitate more efficient degradation of the plastics.
What are the goals of the project?
This project seeks to establish a powerful platform for the discovery and engineering of plastic binding domains. Implementing a new engineering platform is a high-risk, “0-to-1” type project, but the successful completion of the proposed milestones will establish foundational technology for MP remediation. Our specific goals are to 1) demonstrate that yeast display supports MP binding, with flow cytometry assay signals at least 3-fold higher than background signals; 2) establish parallel evaluation of candidate plastic binding domains with a demonstrated throughput of 100 or more samples/day; 3) demonstrate that we can evolve plastic binding domains to recognize MPs with greater than 5-fold improved affinity.
The total requested budget for this one-year project is $100,000.00, inclusive of 10% institutional overhead.
We expect to be able to complete Milestone 1 and establish general proof-of-concept of our proposed system within 4 months. With initial assays established, we will be able to pursue Milestones 2 and 3 in parallel. This would be advantageous because it would enable insights from each milestone to advance the other milestone and increase the chance of overall project success. Ultimately, completion of the 3 milestones will position us to engineer and deploy a versatile set of MP capture agents.
Apr 01, 2024
Demonstration that yeast display is compatible with known protein-based plastic binding domains, with a binding signal at least 3-fold higher than background signal.
Aug 01, 2024
Demonstration of the feasibility of combinatorial evaluation of various binding domains and microplastics (at least 96 separate samples in parallel).
Dec 01, 2024
Demonstration of “evolvability” of plastic binding domains using high throughput screening (at least 5-fold enhancement of binding affinity against a MP of interest).
Meet the Team
The Van Deventer Lab has deep expertise in yeast display and genetic code expansion (an area of synthetic biology). To date, the laboratory has focused on establishing technologies for primary applications in therapeutic and biomedical research settings. We are excited to apply our skillsets to tackle the pressing problems of environmental pollution and climate change.
James Van Deventer
I completed a BS in chemical engineering at Stanford, an MS and PhD in chemical engineering at Caltech, and postdoctoral work at MIT. My research program at Tufts stems from my extensive training in engineering proteins and antibodies, protein-based approaches to targeting the tumor microenvironment, and genetic code manipulation with noncanonical amino acids. The lab has established a unique form of yeast displaying that integrates noncanonical amino acids in search of new classes of therapeutically relevant proteins. We are primarily focused on selectively interfering with enzymes that are dysregulated during cancer progression and in permanently inactivating disease-causing proteins.
Many of my colleagues in chemical engineering are actively engaged in projects that have the potential to lead to a sustainable future. For several years now, I have been thinking carefully about the best ways I might be able to use my expertise to contribute solutions that improve the state of the planet. The protein engineering platform of yeast display is remarkable powerful and versatile. The project proposed in this application is a logical way for my group to leverage our expertise with this platform to improve the health of the planet.
I am privileged to mentor the researchers-in-training of the Van Deventer Laboratory; they are the engine that powers the research of the group. For every student or postdoc that walks through the door of the lab, it is my goal to foster growth and maturation in all aspects of research, from design to experimentation to data interpretation to communication of findings and their significance. I am flattered by having been awarded the “Outstanding Contribution to Graduate Education” by the Tufts University Graduate Student Council in 2021, 2022, and 2023. Investing further in the training of the mentees of my lab by pursuing technologies to mitigate climate change would be a tremendous growth opportunity for the group.
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