Biology subjects

Kwon, E.

Publications and source records attributed to Kwon, E..

3 recordsLinked to original sources

bioRxiv2018

High-throughput retrieval of physical DNA for NGS-identifiable clones in phage display library

In antibody discovery, in-depth analysis of an antibody library and high-throughput retrieval of clones in the library are crucial to identifying and exploiting rare clones with different properties. However, existing methods have several technical limitations such as low process throughput from laborious cloning process and waste of the phenotypic screening capacity from unnecessary repetitive tests on the dominant clones. To overcome the limitations, we developed a new high-throughput platform for the identification and retrieval of clones in the library, TrueRepertoire. TrueRepertoire provides highly accurate sequences of the clones with linkage information between heavy and light chains of the antibody fragment. Additionally, the physical DNA of clones can be retrieved in high throughput based on the sequence information. We validated the high accuracy of the sequences and demonstrated that there is no platform-specific bias. Moreover, the applicability of TrueRepertoire was demonstrated by a phage-displayed single-chain variable fragment (scFv) library targeting human hepatocyte growth factor (hHGF) protein.

bioengineering↗

bioRxiv2018

B7-H1(PD-L1) confers chemoresistance through ERK and p38 MAPK pathway in tumor cells

Development of resistance to chemotherapy and immunotherapy is a major obstacle in extending the survival of patients with cancer. Although several molecular mechanisms have been identified that can contribute to chemoresistance, the role of immune checkpoint molecules in tumor chemoresistance remains underestimated. It has been recently observed that overexpression of B7-H1(PD-L1) confers chemoresistance in human cancers, however the underlying mechanisms are unclear. Here we show that the development of chemoresistance depends on the increased activation of ERK pathway in tumor cells overexpressing B7-H1. Conversely, B7-H1 deficiency renders tumor cells susceptible to chemotherapy in a cell-context dependent manner through activation of the p38 MAPK pathway. B7-H1 in tumor cells associates with the catalytic subunit of a DNA-dependent serine / threonine protein kinase (DNA-PKcs). DNA-PKcs is required for the activation of ERK or p38 MAPK in tumors expressing B7-H1, but not in B7-H1 negative or B7-H1 deficient tumors. Ligation of B7-H1 by anti-B7-H1 monoclonal antibody (H1A) increased the sensitivity of human triple negative breast tumor cells to cisplatin therapy in vivo. Our results suggest that B7-H1(PD-L1) expression in cancer cells modifies their chemosensitivity towards certain drugs and targeting B7-H1 intracellular signaling pathway is a new way to overcome cancer chemoresistance.

cancer biology↗

bioRxiv2016

Unexpected diversity in socially synchronized rhythms of shorebirds

The behavioural rhythms of organisms are thought to be under strong selection, influenced by the rhythmicity of the environment1-4. Such behavioural rhythms are well studied in isolated individuals under laboratory conditions1,5, but free-living individuals have to temporally synchronize their activities with those of others, including potential mates, competitors, prey and predators6-10. Individuals can temporally segregate their daily activities (e.g. prey avoiding predators, subordinates avoiding dominants) or synchronize their activities (e.g. group foraging, communal defence, pairs reproducing or caring for offspring)6-9,11. The behavioural rhythms that emerge from such social synchronization and the underlying evolutionary and ecological drivers that shape them remain poorly understood5-7,9. Here, we address this in the context of biparental care, a particularly sensitive phase of social synchronization12 where pair members potentially compromise their individual rhythms. Using data from 729 nests of 91 populations of 32 biparentally-incubating shorebird species, where parents synchronize to achieve continuous coverage of developing eggs, we report remarkable within- and between-species diversity in incubation rhythms. Between species, the median length of one parents incubation bout varied from 1 - 19 hours, while period length-the time in which a parents probability to incubate cycles once between its highest and lowest value - varied from 6 - 43 hours. The length of incubation bouts was unrelated to variables reflecting energetic demands, but species relying on crypsis (the ability to avoid detection by other animals) had longer incubation bouts than those that are readily visible or actively protect their nest against predators. Rhythms entrainable to the 24-h light-dark cycle were less prevalent at high latitudes and absent in 18 species. Our results indicate that even under similar environmental conditions and despite 24-h environmental cues, social synchronization can generate far more diverse behavioural rhythms than expected from studies of individuals in captivity5-7,9. The risk of predation, not the risk of starvation, may be a key factor underlying the diversity in these rhythms.

animal behavior and cognition↗