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FURTHER OUR KNOWLEDGE

Proposal outline for first projects backed by Clean Research at the University of Washington (UW)

Our team is committed to solving the current research gaps associated with the production of “cell-based” meat. Furthermore, we believe that a single species focus will enable greater advancement of the science and move us closer to solving the problems associated with commercial-scale meat production.

We have selected Zebrafish as our initial species focus due to the wealth of knowledge already available for this species and the relative simplicity of lean fish muscle compared with that of mammalian counterparts and even fatty fish alternatives, as detailed in this draft supplemental table in a commissioned perspective on the future of cell-based meat to be considered for publication following peer review by Cell Press, a top-tier scientific publishing house, for its One Earth publication.

We ultimately envisage the use of genetic modification to produce zebrafish-derived stem cells that possess reduced growth factor requirements and a predisposition for myogenic lineage commitment. In so doing, we will create cells that are cheaper to expand than native cells and easier to induce to differentiate into skeletal muscle cells. However, before such biotechnological advancements can be realized, there are several important steps that must be taken first. We must identify the culture techniques necessary to establish zebrafish stem cell populations that are stable in culture over multiple doubling events. This is essential for the production of cells in the numbers that will be necessary for meat production and has yet to be demonstrated in fish species. Second, we must develop genetic engineering strategies that enable the manipulation of the zebrafish cells such that their nutrient requirements are more modest and the cues necessary to drive them to become muscle are more straightforward. Once these two hurdles have been passed, work towards generating a scalable zebrafish muscle cell can move forward.

As such, our initial research focuses will be split to meet these challenges simultaneously. We will devote part of our efforts and team towards developing zebrafish reporter lines that fluoresce different colors in response to the expression of stem cell and myogenic markers. These cells will enable us to track, in real-time, the stability of pluripotent stem cell phenotypes in culture and calculate the efficiency of our developing differentiation techniques. We will isolate embryonic stem cells from these fish and investigate different culture techniques and media formulations in order to identify those conditions best-suited to maintaining pluripotent fish cells in long-term culture.

Our second focus will be the validation of engineering techniques for the production of stem cell lines with reduced nutrient requirements and a simpler path to myogenic differentiation. While we are committed to focusing on zebrafish, the lack of protocols for generating and maintaining pluripotent fish lines for extended periods means that such work would need to be put on hold until zebrafish lines have been established. To circumvent this issue, we will begin by attempting these goals in human pluripotent lines. Once the zebrafish lines described above are validated, we will then move to adapt progress observed in our human lines to zebrafish cells. This strategy will ensure that work on both areas of this project critical to establishing forward momentum can be started right away and give us the best chance of accelerating the path towards expandable fish stocks. Broad consistency between human and zebrafish embryogenesis engenders confidence that progress made in human cells will be transferrable to fish lines with minimal additional workup.

Our goal is to have these two research gaps answered within the first two years of our efforts on this project, paving the way to establishing our team and extended collaborative at the forefront of cell-based meat research and development.

[UPDATE: JULY 24, 2020] – Our scientific research paper mentioned above has been published. Read more about it in our blog post, Publication in One Earth, or read the paper directly by clicking here: “A More Open Approach Is Needed to Develop Cell-Based Fish Technology: It Starts with Zebrafish”.

 

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