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Publication Metadata only A novel BHLHE41 variant is associated with short sleep and resistance to sleep deprivation in humans(Oxford University Press (OUP), 2014) Pellegrino, Renata; Goel, Namni; Cardinale, Christopher J.; Dinges, David F.; Kuna, Samuel T.; Maislin, Greg; Van Dongen, Hans P. A.; Tufik, Sergio; Hogenesch, John B.; Hakonarson, Hakon; Pack, Allan I.; Department of Chemical and Biological Engineering; Department of Molecular Biology and Genetics; Kavaklı, İbrahim Halil; Faculty Member; Department of Chemical and Biological Engineering; Department of Molecular Biology and Genetics; College of Engineering; 40319Study Objectives: Earlier work described a mutation in DEC2 also known as BHLHE41 (basic helix-loop-helix family member e41) as causal in a family of short sleepers, who needed just 6 h sleep per night. We evaluated whether there were other variants of this gene in two well-phenotyped cohorts. Design: Sequencing of the BHLHE41 gene, electroencephalographic data, and delta power analysis and functional studies using cell-based luciferase. Results: We identified new variants of the BHLHE41 gene in two cohorts who had either acute sleep deprivation (n = 200) or chronic partial sleep deprivation (n = 217). One variant, Y362H, at another location in the same exon occurred in one twin in a dizygotic twin pair and was associated with reduced sleep duration, less recovery sleep following sleep deprivation, and fewer performance lapses during sleep deprivation than the homozygous twin. Both twins had almost identical amounts of non rapid eye movement (NREM) sleep. This variant reduced the ability of BHLHE41 to suppress CLOCK/BMAL1 and NPAS2/BMAL1 transactivation in vitro. Another variant in the same exome had no effect on sleep or response to sleep deprivation and no effect on CLOCK/BMAL1 transactivation. Random mutagenesis identified a number of other variants of BHLHE41 that affect its function. Conclusions: There are a number of mutations of BHLHE41. Mutations reduce total sleep while maintaining NREM sleep and provide resistance to the effects of sleep loss. Mutations that affect sleep also modify the normal inhibition of BHLHE41 of CLOCK/BMAL1 transactivation. Thus, clock mechanisms are likely involved in setting sleep length and the magnitude of sleep homeostasis.Publication Open Access Nanoengineering InP quantum dot-based photoactive biointerfaces for optical control of neurons(Frontiers, 2021) Ulgut, Burak; Department of Electrical and Electronics Engineering; Department of Chemical and Biological Engineering; N/A; Nizamoğlu, Sedat; Kavaklı, İbrahim Halil; Şahin, Afsun; Karatüm, Onuralp; Aria, Mohammad Mohammadi; Eren, Güncem Özgün; Yıldız, Erdost; Melikov, Rustamzhon; Srivastava, Shashi Bhushan; Sürme, Saliha; Doğru-Yüksel, Itır Bakış; Jalali, Houman Bahmani; Faculty Member; Faculty Member; Faculty Member; PhD Student; Researcher; Teaching Faculty; PhD Student; Department of Electrical and Electronics Engineering; Department of Chemical and Biological Engineering; Koç University Research Center for Translational Medicine (KUTTAM) / Koç Üniversitesi Translasyonel Tıp Araştırma Merkezi (KUTTAM); College of Engineering; School of Medicine; Graduate School of Sciences and Engineering; Graduate School of Health Sciences; 130295; 40319; 171267; N/A; N/A; N/A; N/A; N/A; N/A; N/A; N/A; N/ALight-activated biointerfaces provide a non-genetic route for effective control of neural activity. InP quantum dots (QDs) have a high potential for such biomedical applications due to their uniquely tunable electronic properties, photostability, toxic-heavy-metal-free content, heterostructuring, and solution-processing ability. However, the effect of QD nanostructure and biointerface architecture on the photoelectrical cellular interfacing remained unexplored. Here, we unravel the control of the photoelectrical response of InP QD-based biointerfaces via nanoengineering from QD to device-level. At QD level, thin ZnS shell growth (similar to 0.65 nm) enhances the current level of biointerfaces over an order of magnitude with respect to only InP core QDs. At device-level, band alignment engineering allows for the bidirectional photoelectrochemical current generation, which enables light-induced temporally precise and rapidly reversible action potential generation and hyperpolarization on primary hippocampal neurons. Our findings show that nanoengineering QD-based biointerfaces hold great promise for next-generation neurostimulation devices.Publication Open Access Neuropsychiatric symptoms of COVID-19 explained by SARS-CoV-2 proteins' mimicry of human protein interactions(Frontiers, 2021) Department of Chemical and Biological Engineering; N/A; Eser, Hale Yapıcı; Keskin, Özlem; Gürsoy, Attila; Köroğlu, Yunus Emre; Çakmak, Özgür Öztop; Özdemir, Yasemin Gürsoy; Faculty Member; Faculty Member; Department of Chemical and Biological Engineering; Koç University Research Center for Translational Medicine (KUTTAM) / Koç Üniversitesi Translasyonel Tıp Araştırma Merkezi (KUTTAM); School of Medicine; College of Engineering; Graduate School of Sciences and Engineering; 134359; 26605; 8745; N/A; 299358; 170592The first clinical symptoms focused on the presentation of coronavirus disease 2019 (COVID-19) have been respiratory failure, however, accumulating evidence also points to its presentation with neuropsychiatric symptoms, the exact mechanisms of which are not well known. By using a computational methodology, we aimed to explain the molecular paths of COVID-19 associated neuropsychiatric symptoms, based on the mimicry of the human protein interactions with SARS-CoV-2 proteins. Methods: available 11 of the 29 SARS-CoV-2 proteins’ structures have been extracted from Protein Data Bank. HMI-PRED (Host-Microbe Interaction PREDiction), a recently developed web server for structural PREDiction of protein-protein interactions (PPIs) between host and any microbial species, was used to find the “interface mimicry” through which the microbial proteins hijack host binding surfaces. Classification of the found interactions was conducted using the PANTHER Classification System. Results: predicted Human-SARS-CoV-2 protein interactions have been extensively compared with the literature. Based on the analysis of the molecular functions, cellular localizations and pathways related to human proteins, SARS-CoV-2 proteins are found to possibly interact with human proteins linked to synaptic vesicle trafficking, endocytosis, axonal transport, neurotransmission, growth factors, mitochondrial and blood-brain barrier elements, in addition to its peripheral interactions with proteins linked to thrombosis, inflammation and metabolic control. Conclusion: SARS-CoV-2-human protein interactions may lead to the development of delirium, psychosis, seizures, encephalitis, stroke, sensory impairments, peripheral nerve diseases, and autoimmune disorders. Our findings are also supported by the previous in vivo and in vitro studies from other viruses. Further in vivo and in vitro studies using the proteins that are pointed here, could pave new targets both for avoiding and reversing neuropsychiatric presentations.