Sylvia Lee S et al. (2000) East Coast Worm Meeting "Chemosensory modulation of the daf-2/insulin signaling pathway"

Ruvkun GB, Sylvia Lee S

[East Coast Worm Meeting, 2000]

The daf-2 insulin-like, daf-7 TGFb-like, and daf-11 guanylate cyclase signaling pathways regulate dauer formation, whereas daf-2 signaling also controls longevity. Although environmental cues are critical in regulating dauer formation, not much is known about how such environmental signals are integrated into the downstream signaling components. Ciliated sensory neurons play important roles in sensing the environment and epistasis studies have placed cilia mutants upstream of daf-2 and daf-7, but downstream of daf-11, in controlling dauer arrest. Recently, mutations affecting the sensory cilia have also been shown to extend adult lifespan (Apfeld & Kenyon, 1999), a phenotype likely mediated through the daf-2 signaling pathway. Interestingly, double mutants harboring defects in both daf-2 signaling pathway and sensory cilia function exhibit synthetic lethality, possibly due to enhanced daf-2 defects in the mutant animals. We reasoned that genetic screens which identify suppressors of this synthetic lethality would likely further our understanding of the signaling pathway between sensory cilia and the DAF-2 insulin-like receptor and identify outputs from chemosensory neurons which modulate the daf-2 signaling. In a screen of 10,000 EMS-mutagenized daf-2;cilia mutant F2s, we identified ~20 suppressors which exhibited reduced lethality. Progress on the characterization of these mutants will be reported.

Lee, S. et al. (2017) International Worm Meeting "The Novel Utility of the Central Pattern Generator within C. elegans."

Arisaka, K., Lee, S., Hydari, S., Zeng, C.

[International Worm Meeting, 2017]

Central pattern generators, or CPGs, are intrinsic neural rhythms generated in the absence of sensory information. The CPG underlies several diverse and essential behaviors, functionally streamlined and localized for their non-divorceable utility. Traditionally, the CPG has been understood unjustly in the confines of rhythmicity and motor processes. Beginning and framing the C. elegans as a foundational model for the incredible versatility of the basic CPG, we delve into the CPGs unconventional essentiality in sensorimotor integration, substantiation of the physical principles of causality and locality, and its novelty in the context of understanding more complex behaviors, such as human saccadic eye movement. We then discuss the global trends and emergent properties of such rhythms across several organisms that characterize the manifestation of a meaningful patterned neural activity, premised again, in the lens of the highly elucidative neural system of the C. elegans. Penultimately, we demarcate the morphological evolution of the neural information code and neuromodulatory vehicles that biological pressures have enforced on the increasingly complex design of organisms, starring the C. elegans, once again, as the basis and transitional prism for the evolution of this information code from an amplitude based phenomena (graded potential code) to a frequency based phenomena (action potential code). Ultimately, the thematic motif of this article demonstrates the immense utility in understanding the overlooked 302-neuron nervous system of the C. elegans towards unveiling powerful truths in the evolutionary ladder and trending homologies in more complex organisms- of particular interest here, pattern generated behaviors. Our analyses incepts and extends from a compilation of personal lab discoveries and extrinsic literary interpretations of the idiosyncrasies of the C. elegans nervous system, and has been protracted homologies across various Animalia and processes, including the aforementioned saccades in human oculomotor codes.

Lee, S. et al. (2019) International Worm Meeting "A novel repeat-containing protein supports male and female reproduction in C.elegans."

Ahnn, J., Hahn, Y., Durnaoglu, S., Lee, S., Jung, H.

[International Worm Meeting, 2019]

Here, we report that CNP-2 is a novel protein that contains repeats, which are frequently found in proteins displaying flexibility. GFP driven by cnp-2 promoter is highly expressed in the spermatheca, the spermathecal-uterus valve, and male tail, which are elastic. cnp-2 is critical in reproductive processes in both hermaphrodites and male. KSP repeat domain rescued defective phenotypes of cnp-2 lf mutants, although it was distantly related and shows low sequence similarity and identity to CNP-2. Expression of KSP repeats from both worm obscurin and human NF-M reversed most defects in cnp-2 worm mutants in a repeat-number-dependent manner; a greater number of KSP repeats showed more efficient effects. Altogether, the data suggest that cnp-2 is a KRSTPE-rich repeat protein that shares common features with the KSP repeats of NF-M, including regulatory molecular extension to support inter-molecular interactions, and contractile and elastic cellular structures.

Seirin-Lee S et al. (2022) Development "The extra-embryonic space and the local contour are crucial geometric constraints regulating cell arrangement."

Kimura A, Seirin-Lee S, Yamamoto K

[Development, 2022]

In multicellular systems, cells communicate with adjacent cells to determine their positions and fates, an arrangement important for cellular development. Orientation of cell division, cell-cell interactions (i.e. attraction and repulsion) and geometric constraints are three major factors that define cell arrangement. In particular, geometric constraints are difficult to reveal in experiments, and the contribution of the local contour of the boundary has remained elusive. In this study, we developed a multicellular morphology model based on the phase-field method so that precise geometric constraints can be incorporated. Our application of the model to nematode embryos predicted that the amount of extra-embryonic space, the empty space within the eggshell that is not occupied by embryonic cells, affects cell arrangement in a manner dependent on the local contour and other factors. The prediction was validated experimentally by increasing the extra-embryonic space in the Caenorhabditis elegans embryo. Overall, our analyses characterized the roles of geometrical contributors, specifically the amount of extra-embryonic space and the local contour, on cell arrangements. These factors should be considered for multicellular systems.

Lee S et al. (2010) J Am Soc Nephrol "Synergistic interaction between ciliary genes reflects the importance of mutational load in ciliopathies."

Lee S, Weatherbee SD

[J Am Soc Nephrol, 2010]

Lee S et al. (2019) Ecotoxicol Environ Saf "Effect of soil microbial feeding on gut microbiome and cadmium toxicity in Caenorhabditis elegans."

Kim Y, Choi J, Lee S

[Ecotoxicol Environ Saf, 2019]

Microbial community of an organism plays an important role on its fitness, including stress responses. In this study, we investigated the effect of the culturable subset of soil microbial community (SMB) on the stress response of the soil nematode Caenorhabditis elegans, upon exposure to one of the major soil contaminants, cadmium (Cd). Life history traits and the stress responses to Cd exposure were compared between SMB- and Escherichia coli strain OP50-fed worms. SMB-fed worms showed higher reproduction rates and longer lifespans. Also, the SMB-fed worms showed more tolerant response to Cd exposure. Gene expression profiling suggested that the chemical stress and immune response of worms were boosted upon SMB feeding. Finally, we investigated C. elegans gut microbial communities in the presence and absence of Cd in OP50- and SMB-fed C. elegans. In the OP50-fed worms, changes in microbial community by Cd exposure was severe, whereas in the SMB-fed worms, it was comparatively weak. Our results suggest that the SMB affects the response of C. elegans to Cd exposure and highlight the importance of the gut microbiome in host stress response.

Lee S et al. (2021) Int J Mol Sci "AP2M1 Supports TGF- Signals to Promote Collagen Expression by Inhibiting Caveolin Expression."

Shim J, Kim YN, Koo HS, Lee S, Lim GE

[Int J Mol Sci, 2021]

The extracellular matrix (ECM) is important for normal development and disease states, including inflammation and fibrosis. To understand the complex regulation of ECM, we performed a suppressor screening using <i>Caenorhabditis elegans</i> expressing the mutant ROL-6 collagen protein. One cuticle mutant has a mutation in <i>dpy-23</i> that encodes the 2 adaptin (AP2M1) of clathrin-associated protein complex II (AP-2). The subsequent suppressor screening for <i>dpy-23</i> revealed the <i>lon-2</i> mutation. LON-2 functions to regulate body size through negative regulation of the tumor growth factor-beta (TGF-) signaling pathway responsible for ECM production. RNA-seq analysis showed a dominant change in the expression of collagen genes and cuticle components. We noted an increase in the <i>cav-1</i> gene encoding caveolin-1, which functions in clathrin-independent endocytosis. By knockdown of <i>cav-1</i>, the reduced TGF- signal was significantly restored in the <i>dpy-23</i> mutant. In conclusion, the <i>dpy-23</i> mutation upregulated <i>cav-1</i> expression in the hypodermis, and increased CAV-1 resulted in a decrease of TRI. Finally, the reduction of collagen expression including <i>rol-6</i> by the reduced TGF- signal influenced the cuticle formation of the <i>dpy-23</i> mutant. These findings could help us to understand the complex process of ECM regulation in organism development and disease conditions.

Lee S et al. (2001) J Virol "Stabilization but not the transcriptional activity of herpes simplex virus VP16-induced complexes is evolutionarily conserved among HCF family members."

Lee S, Herr W

[J Virol, 2001]

The human herpes simplex virus (HSV) protein VP16 induces formation of a transcriptional regulatory complex with two cellular factors-the POU homeodomain transcription factor Oct-1 and the cell proliferation factor HCF-1-to activate viral immediate-early-gene transcription. Although the cellular role of Oct-1 in transcription is relatively well understood, the cellular role of HCF-1 in cell proliferation is enigmatic. HCF-1 and the related protein HCF-2 form an HCF protein family in humans that is related to a Caenorhabditis elegans homolog called CeHCF. In this study, we show that all three proteins can promote VP16-induced-complex formation, indicating that VP16 targets a highly conserved function of HCF proteins. The resulting VP16-induced complexes, however, display different transcriptional activities. In contrast to HCF-1 and CeHCF, HCF-2 fails to support VP16 activation of transcription effectively. These results suggest that, along with HCF-1, HCF-2 could have a role, albeit probably a different role, in HSV infection. CeHCF can mimic HCF-1 for both association with viral and cellular proteins and transcriptional activation, suggesting that the function(s) of HCF-1 targeted by VP16 has been highly conserved throughout metazoan evolution.

Lee, James S et al. MicroPubl Biol

Sternberg, Paul W, Lee, James S

[MicroPubl Biol, 2019]

One barrier to communication at large face-to-face meetings, especially those focusing on scientific or technical topics, is a rapid way to understand what a person knows and thinks about before initiating a conversation. We have devised and reduced to practice an effective way to accomplish this task, the wearable microPoster. In our experience, we observed that at most scientific meetings, especially once the number of participants passed 100, it is difficult to get productive conversations started with strangers. Thus, conversations tend to initiate among people that already know one another. This tends to exclude newer participants and those who do not have formal speaking slots. The difficulty increases at informal aspects of meetings: coffee breaks, lines for meals, social events, outdoor events in which a prominent speaker might have different clothes and sunglasses and is thus rendered unknown. Poster sessions have long provided a venue for rapid communication and finding participants. These are usually the most productive parts of meetings. Our thinking evolved from jokes about sandwich board posters, in which one walks around with large posters on the front and back, to shirts with printed information. The advent of printed cloth posters provides a practical solution in which a microPoster is cut from the larger poster (ideally cloth), or printed on one or more sheets of standard paper, which are then taped together. A microPoster comprises your name, affiliation (with appropriate granularity determined by the meeting), and a graphical abstract. The goal is to identify yourself in a much more informative way than a nametag. One convenient way to present the microPoster is pinned on your back like a bib number (e.g., as in marathons or dances). We carried out a pilot with ten microPosters at a meeting of 1500 people (Figure 1), and found them to be effective at attracting useful conversation. The addition of a machine readable QR code (e.g., Salt, 2019) is a possible useful addition but we note that the expense in time, money and carbon footprint of a face-to-face meeting is better spent on face-to-face conversations.

Seirin-Lee S et al. (2020) J Math Biol "Transitions to slow or fast diffusions provide a general property for in-phase or anti-phase polarity in a cell."

Seirin-Lee S, Ei SI, Nakahara T, Ishii H, Sukekawa T

[J Math Biol, 2020]

Cell polarity is an important cellular process that cells use for various cellular functions such as asymmetric division, cell migration, and directionality determination. In asymmetric cell division, a mother cell creates multiple polarities of various proteins simultaneously within her membrane and cytosol to generate two different daughter cells. The formation of multiple polarities in asymmetric cell division has been found to be controlled via the regulatory system by upstream polarity of the membrane to downstream polarity of the cytosol, which is involved in not only polarity establishment but also polarity positioning. However, the mechanism for polarity positioning remains unclear. In this study, we found a general mechanism and mathematical structure for the multiple streams of polarities to determine their relative position via conceptional models based on the biological example of the asymmetric cell division process of C. elegans embryo. Using conceptional modeling and model reductions, we show that the positional relation of polarities is determined by a contrasting role of regulation by upstream polarity proteins on the transition process of diffusion dynamics of downstream proteins. We analytically prove that our findings hold under the general mathematical conditions, suggesting that the mechanism of relative position between upstream and downstream dynamics could be understood without depending on a specific type of bio-chemical reaction, and it could be the universal mechanism in multiple streams of polarity dynamics of the cell.