Mechanosensitive channels transduce physical force into electrochemical signaling and play essential roles in touch, hearing, and proprioception. Several classes of mechanosensitive channels have been identified, including the degenerin and epithelial Na+ channels (DEG/ENaCs), transient receptor potential (TRP) proteins, transmembrane channel-like (TMC) proteins, and Piezo ion channels. Mechanosensitive ion channels are not only expressed in sensory systems but also in various tissues throughout the body to regulate numerous developmental processes, such as vascular development and erythrocyte volume homeostasis. However, the involvement of mechanosensitive channels in neuronal development is not understood. In this talk, I will present our recent works about how DEG/ENaC mechanosensitive channels regulate the growth and branching of dendrites during neuronal development and what their roles are in the proprioceptive system in C. elegans.

Plastic waste poses an ecological challenge and enzymatic degradation offers a green and sustainable route for plastic waste recycling. Poly (ethylene terephthalate) (PET) accounts for 12% of global solid waste, and a circular carbon economy for PET is theoretically attainable through rapid enzymatic depolymerization followed by repolymerization or valorization into other products. However, the practical application of PET hydrolases has been hampered by their lack of robustness, slow reaction rates and inability to directly use untreated postconsumer plastics.

Herein, we report the use of a structure-based, machine learning algorithm to engineer a robust and active PET hydrolase. Our best resulting mutant (FAST-PETase: Functional, Active, Stable, and Tolerant PETase) exhibits superior PET-hydrolytic activity relative to both wild-type and engineered alternatives. We demonstrate that whole, untreated, post-consumer PET from 51 different plastic products can all be completely degraded by FAST-PETase within one week, and in as little as 24 hours. FAST-PETase can also depolymerize untreated, amorphous portions of a commercial water bottle and an entire thermally pretreated water bottle at 50 ºC. Moreover, we demonstrate a closed-loop PET recycling process by using FAST-PETase and resynthesizing PET from the recovered monomers. Collectively, our results demonstrate a viable route for enzymatic plastic recycling at the industrial scale.

DNA double strand breaks (DSBs) are highly toxiclesions that can lead to genomic instability. Preciseregulation of DSBs repair is crucial to preserve genomeintegrity, as failure to repair DSBs properly is known todrive tumorigenesis and several human geneticsyndromes. In this seminar, Dr. Liang will describe newhigh throughput genomics and animal modelingapproaches to study the DSBs occurrence and repair.He has developed neural blastocyst complementation(NBC) system, which allows the introduction of geneticalterations into embryonic stem (ES) cells that used togenerate a complete mouse forebrain. He has alsoexploitedhighthroughputgenomicanewtranslocation sequencing method (HTGTS-JoinT-seq)to capture DNA ends arising from a solitary DSBs athigh resolution. Finally, Dr. Liang has applied thesenew methods to elucidate the implications of DSBs andunderlying mechanisms of genomic instability.

We learn and remember multiple new experiencesthroughout the day. The neural principles enablingcontinuous rapid learning and formation of distinctrepresentationsofnumeroussequentiaexperiences without major interference are notunderstood. To understand this process, weinterrogated ensembles of hippocampal place cellsas rats explored 15 novel linear environmentsinterleaved with sleep sessions over continuous16-hour periods. Remarkably, we found that apopulation of place cells were selective toenvironment orientation and topology.Thisorientation selectivityproperty biasedthenetwork-level discrimination and re/mappingbetweenmultipleenvironments.Novelenvironmental representations emerged rapidly asmore generic, but repeated experience within theenvironments subsequently enhanced theirdiscriminability. Generalization of prior experiencewithdifferentenvironmentsconsequentlyimproved network predictability of future novelenvironmental representations via strengthenedgenerative predictive codes. These coding schemesreveal a high-capacity, high-efficiency neuronalframework for rapid representation of numeroussequentialwithexperiencesoptimaldiscrimination-generalization balance and reducedinterference.

Neuromuscular junctions (NMJs) are synapses formedbetween motoneurons and muscle fibers, andcharacterized with high density of acetylcholinereceptors (AChRs) at postsynaptic membrane. Rapsyna postsynaptic adaptor protein, anchors AChR to thecytoskeleton and induces AChR cluster formation. Ourrecent result shows that rapsyn is an E3 ligase whichneddylates subunits of AChR and promotes AChRclustering. However, how these processes are regulatedremains unclear. To this end, we firstly focus on rapsynmutationsidentifiedin congenital myastheniasyndromes (CMSs)，a group of heterogeneous NMJdisorders characterized with muscle weakness andfatigues. Through studying disease-related mutation.we found that rapsyn become tyrosine-phosphorylatedin response to upstream signaling. Phosphorylation ofrapsyn promotes its self-association and E3 ligaseactivity and thus promotes AChR clustering, suggestinga signaling molecule of rapsyn. Moreover, we combinedbiochemical assay with cellular culture and in vivoassay and found that rapsyn undergoes liquid-liquidphase separation (LLPS) and condensates intoliquid-like assemblies. Such assemblies can recruitAChRs, cytoskeletal proteins, and signaling proteins forpostsynapticdifferentiation, revealing a novelmechanism of rapsyn in postsynaptic assembly.

The goal of my research is to understand the molecular and geneticregulatory circuits that control cell proliferation and differentiationduring development of multicellular organisms. Using Drosophila as amodel system, my lab focuses on the following two major researchtopics in the past decade: (1) investigating the molecular and cellularmechanisms that control stem cell biology in Drosophila ovary andgut; and (2) creating and optimizing novel genetic tools and resourcesto facilitate sophisticated analyses of Drosophila genome. Thesynergistic effects between two research projects allowed us to gaininsights into the molecular mechanisms that control stem-cell renewain ovary and intestine of Drosophila. I will briefly introduce my labachievements in the past five years.

Protein posttranslational modifications (PTMs) play essential roles inthe regulation of almost all biological processes, ranging from DNAreplication and gene expression to metabolism. The dysregulation ofproteins PTMs often leads to human diseases such as cancer andneurodegenerative diseases. Therefore, it is of great importance toreveal the biological significance of protein PTMs and their regulatorymechanisms. Benefiting from the rapid development of massspectrometry technology, the number of known PTMs has increasedrapidly. However, only a handful of protein PTMs have beenextensively studied, while the cellular mechanisms and functions ofmany other PTMs, particularly those newly identified ones, remainspoorly understood. In this talk, I will present the new strategies anddiscoveries on the biological significance and regulation mechanismof several novel protein PTMs.

The immune response is a hallmark of cancer playingcritical roles in both pathogen defense and tumorprogression, operating through intracellular protein-proteininteraction networks organized in space and time. Abnormalprotein-protein interactions and signaling activations lead todysregulated cell-cell interactions and diseases. By usingproximity labeling mediated by engineered ascorbic acidperoxidase (APEX) and genetic mouse models, we uncoveredprotein complexes that are essential for antiviralimmuneactivation,cancer metastasis, immune cell-state transitionand cell-cell interactions in the tumor microenvironment. Inlight of the unsurpassable flexibility and spatiotemporalprecision to manipulate cell physiology, optogenetics hasbeen gaining rapid momentum in both neuronal cells andnon-excitable cells. To modulate immune cell function at ahigh spatiotemporal resolution in vivo, we devised a series ofnano-optogenetic tools for the optical control of effectorfunctions of immune cells and light-inducible tumor killing invivo. To continue my interests in immune-related diseases, lpropose to apply pooled screen, single cell and spatialtechnologies to dissect cell circuits and gene programsgoverning the progression of immune-related diseases.

Rail and urban transit systems often serve a large number of passengerson a daily basis and play an important role in supporting economicactivities. This presentation will discuss how to utilize modeling anddata analysis tools to improve our understanding and performanceof rail or urban transit systems. In particular, this presentation will firstdiscus data mining and modeling techniques for quantifying mobilitypatterns and demand prediction in rail/transit systems. Then, givencertain levels of demand information, pricing and service networkdesign problems in rail/transit systems will be presented. A fewexamples on game-theoretical models and network design models forpassenger-freight integrated transit/rail system will be illustrated. Inaddition, several empirical studies that examine the impacts of raildevelopment on accessibility, economy and equity will be discussedwhere the joint effect of rail development and megalopolis policy willalso be covered. In summary, this presentation illustrates with exampleshow modeling and analysis tools can be applied to rail and urban transitsystems for better policy and decision making.