We study cultured meat.
We are part of the Volcani center for Agriculture Research
positioned in the Agriculture Faculty in Rehovot
The Genetic Basis of Proliferation and Differentiation in Cultured Meat Production
Cultured meat is a promising solution for meat production that will reduce environmental burden and animal suffering. Current challenges in producing cultured meat is the efficiency of the process, which is dictated by the proliferation capacity of the origin cells and the differentiation efficiency toward the target cell types. our lab aims to much advance the science and technology of meat culturing through the use of modern genomics technologies and new concepts regarding the genetic regulation of cellular proliferation and differentiation. At the heart of our studies is the use of genome manipulation and editing in screens of mesenchymal stem cells isolated from bovine to search for genes and pathways controlling the proliferation rate and differentiation process into muscle cells. It is expected that the fruits of this research will much advance our ability to cultivate meat and that more general insights would apply to additional agricultural crops.
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Dynamic changes in tRNA modifications and abundance during T-cells activation
The tRNA pool determines the efficiency, throughput, and accuracy of translation. Previous studies have identified dynamic changes in the tRNA (transfer RNA) supply and mRNA (messenger RNA) demand during cancerous proliferation. Yet dynamic changes may also occur during physiologically normal proliferation, and these are less well characterized. We examined the tRNA and mRNA pools of T cells during their vigorous proliferation and differentiation upon triggering their antigen receptor. We observed a global signature of switch in demand for codons at the early proliferation phase of the response, accompanied by corresponding changes in tRNA expression levels. In the later phase, upon differentiation, the response of the tRNA pool relaxed back to the basal level, potentially restraining excessive proliferation. Sequencing of tRNAs allowed us to evaluate their diverse base-modifications. We found that two types of tRNA modifications, wybutosine and ms2t6A, are reduced dramatically during T cell activation. These modifications occur in the anticodon loops of two tRNAs that decode “slippery codons,” which are prone to ribosomal frameshifting. Attenuation of these frameshift-protective modifications is expected to increase the potential for proteome-wide frameshifting during T cell proliferation. Indeed, human cell lines deleted of a wybutosine writer showed increased ribosomal frameshifting, as detected with an HIV gag-pol frameshifting site reporter. These results may explain HIV’s specific tropism toward proliferating T cells since it requires ribosomal frameshift exactly on the corresponding codon for infection. The changes in tRNA expression and modifications uncover a layer of translation regulation during T cell proliferation and expose a potential tradeoff between cellular growth and translation fidelity.