@article {47810,
	title = {Mathematical model of the multi-amino acid multi-transporter system predicts uptake flux in CHO cells},
	journal = {Journal of Biotechnology},
	volume = {344},
	year = {2022},
	month = {JAN},
	pages = {40-49},
	type = {Article},
	abstract = {Supply and uptake of amino acids is of great importance to mammalian cell culture processes. Mammalian cells such as Chinese hamster ovary (CHO) cells express several amino acid (AA) transporters including uniporters and exchangers. Each transporter transports multiple AAs, making prediction of the effect of changed medium composition or transporter levels on individual AA transport rate challenging. A general kinetic model for such combinatorial amino acid transport, and a simplified analytical expression for the uptake rate as a function of amino acid concentrations and transporter levels is presented. From this general model, a CHO cell-specific AA transport model, to our knowledge the first such network model for any cell type, is constructed. The model is validated by its prediction of reported uptake flux and dependencies from experiments that were not used in model construction or parameter estimation. The model defines theoretical conditions for synergistic/repressive effect on the uptake rates of other AAs upon external addition of one AA. The ability of the CHO-specific model to predict amino acid interdependencies experimentally observed in other mammalian cell types suggests its robustness. This model will help formulate testable hypotheses of the effect of process changes on AA initial uptake, and serve as the AA transport component of kinetic models for cellular metabolism.},
	keywords = {Amino acid transport, CHO cell, Exchanger, mathematical model, Multiple transporters},
	issn = {0168-1656},
	doi = {10.1016/j.jbiotec.2021.12.003},
	author = {Sreejan, Ashley and Gadgil, Mugdha and Gadgil, Chetan J.}
}
@article {48131,
	title = {SUMOylation of dorsal attenuates Toll/NF-kappa B signaling},
	journal = {Genetics},
	volume = {221},
	year = {2022},
	month = {JUL },
	type = {Article},
	abstract = {<p>
	In Drosophila, Toll/NF-kappa B signaling plays key roles in both animal development and in host defense. The activation, intensity, and kinetics of Toll signaling are regulated by posttranslational modifications such as phosphorylation, SUMOylation, or ubiquitination that target multiple proteins in the Toll/NF-kappa B cascade. Here, we have generated a CRISPR-Cas9 edited Dorsal (DL) variant that is SUMO conjugation resistant. Intriguingly, embryos laid by dl(SCR) mothers overcome dl haploinsufficiency and complete the developmental program. This ability appears to be a result of higher transcriptional activation by DLSCR. In contrast, SUMOylation dampens DL transcriptional activation, ultimately conferring robustness to the dorso-ventral program. In the larval immune response, dl(SCR) animals show an increase in crystal cell numbers, stronger activation of humoral defense genes, and high cactus levels. A mathematical model that evaluates the contribution of the small fraction of SUMOylated DL (1-5\%) suggests that it acts to block transcriptional activation, which is driven primarily by DL that is not SUMO conjugated. Our findings define SUMO conjugation as an important regulator of the Toll signaling cascade, in both development and host defense. Our results broadly suggest that SUMO attenuates DL at the level of transcriptional activation. Furthermore, we hypothesize that SUMO conjugation of DL may be part of a Ubc9-dependent mechanism that restrains Toll/NF-kappa B signaling.</p>
},
	keywords = {Drosophila, haploinsufficiency, innate immunity, SUMO, transcription},
	issn = {0016-6731},
	doi = {10.1093/genetics/iyac081},
	author = {Hegde, Sushmitha and Sreejan, Ashley and Gadgil, Chetan J. and Ratnaparkhi, Girish S.}
}
