Fun fact: One of the first things Jens did when he arrived in Boston was to buy a bike. Molecular Neurobiology and RNA Metabolism Laboratory. and Kornblihtt A.R. We are particularly interested on the role of circular RNAs (circRNAs) at the molecular and neural levels as well as the mechanisms underlying circadian clocks. For example, we identified a number of ion channels that either directly or indirectly regulate stem cell proliferation. and Torres H.N. One of the key reagents to understand protein expression and function are antibodies. Sher also loves watching European football and is a die-hard Chelsea football club fan. Jess earned her PhD in Neuroscience working in the laboratory of Dr. Thomas Clandinin, utilizing the Drosophila visual system and forward genetics to study synapse development and axon degeneration. Advantages of CRISPRi as compared with RNAi are that the level of knockdown can be more tightly controlled and the system appears to have reduced off-target effects. Brown S.A., Ripperger J., Kadener S., Fleury-Olela F., Vilbois F., Rosbash M. and Schibler U. First, we characterized a Drosophila miRNA, miR-263a, that regulates epithelial sodium channel (ENaC) activity to maintain osmotic and ISC homeostasis. Copyright 2017 | Privacy policy | Legal statements Molecular Interaction Search Tool) for mining, visualization and analysis of network data, for mining protein post-translational modification (PTM) data and comparison of PTM data across species and. dsGFP, because of its short half-life, captures real-time signaling, while stable RFP labels cells in which signaling activity has occurred. Protocol. We use Drosophila as a model system to characterize the mechanisms underlying communication between cells, tissues, and organs. Working under the mentorship of Dr. Beth Lawlor, April focused on understanding how hijacking of normal developmental pathways lead to heterogeneity and cell state plasticity in Ewing sarcoma. Regulation of alternative splicing by a transcriptional enhancer through RNA pol II elongation. Rabin A, Zaffagni M, Ashwal-Fluss R, Patop IL, Jajoo A, Shenzis S, Carmel L, Kadener S. Extensive tissue-specific expression variation and novel regulators underlying circadian behavior. Fun fact:Almost all of Johns socks are Christmas themed! Kadener, Sebastian / Brandeis University Publications. One point of focus for DRSC-BTRR efforts is establishment of CRISPR pooled screening in cell lines from mosquito vectors of infectious diseases. Biol., The University of Buenos Aires, Buenos Aires, Argentina, Ph.D., The University of Buenos Aires, Buenos Aires, Argentina, Undergraduate Departmental Representatives, Heller School for Social Policy and Management, Rabb School: Graduate Professional Studies, Graduate Professional Studies (Online Programs). Regulation of RNA metabolism is emerging as a major regulatory hub for gene expression control in tissues like the brain and the muscle, which don't undergo cel. I am in the Class of 2024 studying neuroscience and biology. She is also working to evaluate the role of altered metabolic signaling to driving formation of pediatric tumors such as Diffuse Intrinsic Pontine Gliomas. Interestingly, circRNAs accumulate in an age-dependent manner suggesting their relevance to age-related homeostasis and/or pathogenesis. Rosenstiel332781-736-4915skadener@brandeis.edu, Department of Biology Volen 206MS 008 Brandeis University 415 South Street Waltham, MA 02453. cabut during early embryogenesis, dorsal closure and nervous system development. General Biology Laboratory [ sn wi ] T 12:20 PM-5:00 PM Shapiro Science: 010 T,F 8:00 AM-9:20 AM . Samar was awarded the Neubauer doctoral fellowship . We showed that miRNAs have a key role in providing robustness to the circadian system both during development and in adults. Chikne V.*, Doniger T.*, Bartok O. For example, little is understood about how the simultaneous growth and differentiation of different tissues and organs are coordinated and how the development of different cell types and tissues is integrated within an organ. Rosi is attending the structural MS workshop in Finland. Proximity Labeling: Characterizing the proteome composition of organelles and subcellular regions of living cells can facilitate the understanding of cellular organization as well as protein interactome networks. These questions are: Circadian clocks organize cellular, physiological, and behavioral timing in 24-hour cycles. Fun fact: Outside the lab, Adam is an avid soccer fan and enjoys watching the English Premier League. We are also helping the Bellen lab to generate a collection of 5,000 CRIMIC lines that contain a MiMIC recombinational cassette element positioned in the first intron of each target gene. She makes a mean pour over coffee, and her favorite animal is a tie between a sloth and a quokka. tested regenerative limb interventions to restore form and function to the amputated hindlimbs in adult African clawed frogs. The challenge is now to understand how these pathways intersect and cooperate, as it is not clear if some pathways regulate the activity of others, or if they act concomitantly. Alternative splicing regulates biogenesis of miRNAs located across exon-intron junctions. Cold Spring Harbor Laboratory Online. What are the neural and molecular basis of temperature adaptation and compensation? Cramer P., Srebrow A., Kadener S., Werbajh S., de la Mata M., Melen G., Nogues G. and Kornblihtt AR. Its very important for us! Hanan M., Soreq H. and Kadener S. CircRNAs in the brain. Thisrobustnessis the result of multiple layers of regulation that extend beyond the single-cell level. *, Eliaz D.*, Cohen Chalamish S., Tschudi C., Unger R., Hashem Y., Kadener S. and Michaeli S. Pseudouridylation in. What are the key functions of these molecules in the brain and during aging? Anna developed a fascination for cancer biology while working towards her bachelors degree at Lund University, Sweden. Chikne V.*, Doniger T.*, Bartok O. Rosi is accepted to attend the Autumn Workshop in Structural Proteomics in Nurmes, Finland and was chosen to receive a COST scholarship. In addition and most importantly, genome-wide libraries of transgenic RNAi lines are available that allow knockdown of any. . First, we developed a new method to visualize the dynamic activation of pathway activities. Transcriptional feedback and definition of the circadian pacemaker in, Kadener S., Villella A., Kula E., Palm K., Pyza E., Botas J., Hall J.C. and Rosbash M. Neurotoxic protein expression reveals connections between the circadian clock and mating behavior in. Genome-Wide Analysis of Light- and Temperature-Entrained . Litovchenko M, Meireles-Filho ACA, Frochaux MV, Bevers RPJ, Prunotto A, Anduaga AM, Hollis B, Gardeux V, Braman VS, Russeil JMC, Kadener S, Dal Peraro M, Deplancke B. Host-derived circular RNAs display proviral activities in Hepatitis C virus-infected cells. 1, Artyomov M., Shishkin A., Kadri S., Zhu X., Gutman M., Garber M.* and Kadener S.* Defining the 5 and 3 landscape of theDrosophilatranscriptome with ExoCAGE and RNaseH-seq. Zaffagni M, Kadener S. NEAT1 is overexpressed in Parkinson's disease substantia nigra and confers drug-inducible neuroprotection from oxidative stress. High-accuracy determination of internal circadian time from a single blood sample. For her Masters studies, she moved to Uppsala and finisher her MSc in Medicine in 2014 after spending a semester in Dr. Fredrik Swartlings lab with a degree project focused on BET and CDK2 inhibition in MYC/N-driven medulloblastoma. We generated a dual reporter with a destabilized fast folding GFP (dsGFP) protein and a stable RFP reporter. Acquiring answers to these fascinating questions requires a deep understanding of the mechanisms by which cells integrate signals received from their inner selves, neighboring cells, other organs and the environment. I am studying potential applications of the CRISPR/Cas13 system. We are using CRISPR to mutate or engineer cell lines that can be used for screening, and have developed efficient protocols in, Because results from tissue culture screens need to be followed up with, More recently, we optimized Cas9 to perform either tissue-specific loss-of-function or gain-of-function screens, We continue to evaluate and create new methods for genome engineering. Sebastian Kadener Activities Collapse all Works (11) sort Sort The chromatin factor ROW cooperates with BEAF 32 in regulating longrange inducible genes EMBO reports 2022-12-06 | Journal article DOI: 10.15252/embr.202254720 Contributors : Neta Herman; Sebastian Kadener; Sagiv Shifman Show more detail Source : Crossref Our main accomplishments regarding biological questions have been in the areas of canonical signaling pathway organization, cell polarity establishment, gut regeneration and homeostasis, and inter-organ communication. Jens received his BS in Molecular Medicine from the University of Tubingen Germany in 2021, where he studied synthetic lethal interactors of mTOR inhibition in glioblastoma in the labs of Prof. Ghazaleh Tabatabai and Dr. Daniel Merk. Molecular Neurobiology and RNA metabolism. M.Sc., The University of Buenos Aires, Buenos Aires, Argentina Ph.D., The University of Buenos Aires, Buenos Aires, Argentina. A slow RNA polymerase II affects alternative splicing in vivo. Studying the neuronal functions of circular RNA. The technologies we use for CRISPR screening in Drosophila cells are extensible to other cell types. We demonstrated that shRNAs are more efficient and specific than long dsRNA when expressed as transgenes, and generated a genome scale collection of >13,000 lines covering 75% of the genome in our optimized VALIUM vectors (85% of highly conserved genes). Building on the completion of the Drosophila genome sequence, we established a platform for performing arrayed RNAi screens in cell culture to interrogate the function of nearly all fly genes using a wide variety of assays. Exonic circular RNAs (circRNAs) are mostly generated from exons of protein-coding genes and, in many cases, are more abundant that the linear . This plasticity is the result of the existence of very efficient input pathways that convey the external signals into the core oscillator machinery. In the Bandopadhayay Lab, Leslie has been able to combine her background in cancer cell metabolism with genomic, transcriptomic and gene editing approaches to understand the biology of pediatric brain tumors and elucidate mechanisms of resistance to targeted therapies such as BET-bromodomain inhibition. The Kadener laboratory studies how molecular processes in the brain determines behavior with a special emphasis on RNA metabolism. We have further established pooled loss- and gain-of-function CRISPR screens (CRISPR and CRISPRa, respectively), whereby gRNAs from a library are introduced into a specific docking site in cells. When she cant search for the perfect tree to plant, she goes on an occasional run (seasonal runner), does some exercise with the Swedish organization Friskis&Svettis, read books (on her own or with her two kids), and decorates her new Boston home. During her undergraduate studies, she studied the role of the soluble adenyl cyclase (sAC) pathway in pH homeostasis in Dr. Katie Barotts lab. Coupling of transcription with alternative splicing: RNA pol II promoters modulate SF2/ASF and 9G8 effects on an exonic splicing enhancer. An early ancestor in the evolution of splicing: a. Nogues G., Kadener S., Cramer P., de la Mata M., Fededa J.P., Blaustein M., Srebrow A. and Kornblihtt A.R. Hu, Comjean, Attrill, Antonazzo, Jim Thurmond, Li, Chao, Mohr, Brown, Perrimon Selected for Faculty of 1000 (Factor 3 Recommended). Send us removal request. . Sebastian Kadener Prof. Nac. Statuses. I am interested in studying circular RNAs and neurological disorders. Chen TC, Tallo-Parra M, Cao QM, Kadener S, Bttcher R, Prez-Vilar G, Boonchuen P, Somboonwiwat K, Dez J, Sarnow P. A lncRNA survey finds increases in neuroprotective LINC-PINT in Parkinson's disease substantia nigra. *, Afik S., Menet J., Wolfson V., Weissbein U., Haimovich D., Gafni C., Friedman N., Rosbash M. and Kadener S. . Lic. bioRxiv 2023.02.20.529262; doi: Copyright 2023 The President and Fellows of Harvard College. PERIOD1-associated proteins modulate the negative limb of the mammalian circadian oscillator. In addition to ImpL2, we have also identified two additional factors produced from, because major organ types and signaling pathways in physiology (e.g. Nucleic Acids Research47(11): e95; 1-16 (2017). Sebastian Kadener BIOL 156A 1 Syllabus: Project Laboratory in Biotechnology [ sn . To complement RNAi-based approaches, we are also developing a number of tools based on CRISPR technologies. neta.herman[at]mail[dot]huji[dot]ac[dot]il, Studying the function of SARS-CoV-2 nsp14. Dana joined the Bandopadhayay Lab in 2021 where is she working to apply single-cell methods to evaluate the heterogeneity of pediatric gliomas, and to understand spatial associations. We showed that their translation is mediated by IRES-like sequences, is enhanced in response to starvation and happens in association with membranes and in synapses. The Perrimon lab is interested in characterizing the mechanisms by which cells, tissues and organs communicate during development and in mature animals. She then obtained her the PhD from Cancer Biology PhD program at the University of Michigan in 2022. What are the key functions of these molecules in the brain and during aging? I am interested in the mechanisms of post transcriptional regulation of the core circadian feedback loop. I am a PhD student in the lab since 2018 after graduating from The College of Wooster. A polar mechanism coordinates different regions of alternative splicing within a single gene. . Antibodies allow protein visualization by immunostaining, biochemical study by immunoprecipitation and western blot, and proteomic study by IP-MS. View 129 related references Ask authors/readers for more resources. CRISPR-generated mutant cell lines, in combination with RNAi, provide a robust platform for combinatorial screening. Our most popular tools are: DIOPT, an integrative tool for ortholog predictions among major model organisms. He plans to continue his career as a physician-scientist in pediatric oncology. Simchovitz A, Hanan M, Yayon N, Lee S, Bennett ER, Greenberg DS, Kadener S, Soreq H. A Parkinson's disease CircRNAs Resource reveals a link between circSLC8A1 and oxidative stress. September 2018. Associate Professor, Brandeis University. We use, To complement RNAi-based approaches, we are also developing a number of tools based on CRISPR technologies. Circadian clocks are also exceptionallyplasticas they can quickly and specifically adjust to specific environmental cues. S Kadener, P Cramer, G Nogus, D Cazalla, M de la Mata, JP Fededa, . * Corresponding authors. Kadener S., Fededa J.P., Rosbash M. and Kornblihtt A.R. In a collaboration with Sebastian Kadeners lab at Brandeis, we generated a new set of PspCas13b and RfxCas13d expression constructs that can be used to target RNA in cells and in vivo. Selected for Faculty of 1000 (Factor 6 Must Read). Nogues G., Kadener S., Cramer P., Bentley D. and Kornblihtt A.R. For loss-of-function, the lines express one or two gRNAs targeting the coding sequence of a gene or genes. In response to tissue damage reagents such as paraquat and bleomycin, TrpA1 mediates calcium influx, which in turn activates Ras/MAPK pathway and induces stem cell proliferation. High-accuracy determination of internal circadian time from a single blood sample. Further, our work and that of others has suggested functions of these moleculesin vivo. Pamudurti N., Bartok O., Jens O., Ashwal-Fluss R., Stottmeister C., Ruhe L., Hanan M., Wyler E., Perez-Hernandez D., Ramberger E., Shenzis S., Samson M., Dittmar G., Landthaler M., Chekulaeva M., Rajewsky N. and Kadener S. Translation of circRNAs. PANGEA: A New Gene Set Enrichment Tool for Drosophila and Common Research Organisms We have several efforts underway to produce new binary expression system reagents by CRISPR-mediated knock-in, including split-GAL4, LexA, and QF. Moreover, we also showed that the neural and molecular circadian systems compensate and interact with each other. News. * Corresponding authors. Simchovitz A, Hanan M, Niederhoffer N, Madrer N, Yayon N, Bennett ER, Greenberg DS, Kadener S, Soreq H. Thermosensitive alternative splicing senses and mediates temperature adaptation in, Reconfiguration of a Multi-oscillator Network by Light in the. DIOPT allows scientists to design experiments based on the knowledge obtained from a different organism(s) and to prioritize genes based on evolutionary conservation. For his senior clinic project, John worked with HRL Laboratories to create an algorithm for electrostatically tuning quantum dots using neural networks for quantum computers. The work is a collaboration between Dr. Kadener's lab and Prof. Nikolaus Rajewsky from the Max Dellbruck Institute, Berlin, Germany. For example, the vertebrate CNS receives information regarding the status of peripheral metabolic processes via hormonal signaling and direct macromolecular sensing. Elife 8. What are the neural and molecular basis of temperature adaptation and compensation? We renamed the center DRSC/TRiP-Functional Genomics Resources to better represent our current capabilities. Interestingly, JAK/STAT signaling in the muscle or fat body directly triggers the expression of ImpL2, which in turn impairs local insulin signaling and its associated energy balance. The EMBO journal 20 (20), 5759-5768, 2001. Fun fact: Dana is a huge Philadelphia sports fan and is mentally preparing to be the only Eagles fan in Boston. Further, our work and that of others has suggested functions of these moleculesin vivo. Adam grew up in Ethiopia and moved to Bremen, Germany where he received his B.Sc and M.Sci in Biochemistry and Cell Biology from Jacobs University which was his very first exposure to the exciting field of epigenetics. Gene Expression Omnibus (GEO) is a database repository of high throughput gene expression data and hybridization arrays, chips, microarrays. Before joining the Bando Lab, John worked as a High Frequency Trader. 10.1261/rna.068692.118 References. Are circRNAs involved in neurodevelopmental and neurodegenerative diseases? Sebastian Kadener Principal Investigator M.Sc., The University of Buenos Aires, Buenos Aires, Argentina Ph.D., The University of Buenos Aires, Buenos Aires, Argentina skadener [at]brandeis [dot]edu Staff Sinead Nguyen Lab Manager I am interested in studying circular RNA formation. Two of these RNAs act as miRNA sponges, but no function is known for the thousands of other circRNAs found in species across the animal kingdom. Eric studied how the interaction of cell surface proteins expressed by different cell types can regulate blood vessel formation in normal cells and tumors. Selected for Faculty of 1000 (Factor 3.0 Recommended). S Kadener, P Cramer, G Nogus, D Cazalla, M de la Mata, JP Fededa, . Additionally, many of the mechanisms by which growth factortriggered signaling events intersect with cell metabolism, which is regulated by nutrients, hormones and stress, remain to be identified. Patop, Ines Lucia; Kadener, Sebastian . Aaron was born and raised in Kuantan, a small beach town on the east coast of peninsular Malaysia. Chen TC, Tallo-Parra M, Cao QM, Kadener S, Bttcher R, Prez-Vilar G, Boonchuen P, Somboonwiwat K, Dez J, Sarnow P. A lncRNA survey finds increases in neuroprotective LINC-PINT in Parkinson's disease substantia nigra. Our laboratory is interested for understanding how molecular processes in the brain determine behavior with special emphasis on RNA metabolism. For example, we showed that circRNA biogenesis competes with canonical splicing, showing that circRNAs can function incisas RNA traps. We have also generated stable nuclease-dead Cas9 activator (dCas9a) cell lines that can be used, after transfection with gRNAs, to perform overexpression screens - thus complementing loss of function screens. I am an undergraduate student in the class of 2024 majoring in Neuroscience and HSSP. The current model postulates that circadian oscillators keep time by complex transcriptional and post-transcriptional feedback loops. @skadener. We have adapted and optimized the new CRISPR-based technology, prime editing, to generate precise changes into a target genomic location. This collection is available to the community through the Bloomington Drosophila Stock Center. Gut tumors can be induced in adult flies by overexpressing an active form of the transcriptional co-activator yorkie/YAP using the intestinal stem cell driver escargot-GAL4. In a collaboration with Sebastian Kadeners lab at Brandeis, we generated a new set of PspCas13b and RfxCas13d expression constructs that can be used to target RNA in cells and in vivo. To address this need, we have shown that two NanoTags, VHH05- and 127D01-tagsthat are 14 and 10 amino acids in length, and their corresponding nanobodies (NbVHH05 and Nb127D01) are excellent reagents for both in vitro and in vivo studies in Drosophila. at USC we have extended this approach to the mouse. The current model postulates that circadian oscillators keep time by complex transcriptional and post-transcriptional feedback loops. Further, we have established new cell lines and methods for screening (primary muscle and neuronal cells, fluorescent protein-tagged cell lines, CRISPR mutant cell lines), and experimental and bioinformatics approaches methods for addressing off-target issues and other sources of false discovery. Strikingly, these phenotypes are reminiscent of the pathophysiology of cystic fibrosis (CF), as in CF the non-functional CF transmembrane conductance regulator (CFTR) increases ENaC activity resulting in chronic dehydration of the intraluminal surface liquid in organs such as kidney, colon, lung and sweat glands. Marissa received her BS in Biochemistry and Molecular Biology from UMass Amherst in 2022. The tagged endogenous proteins can then be isolated for further analysis by MS. To analyze protein-protein interactions or identify components that localize to discrete subcellular compartments, we developed tools based on. Fun fact: Maddie is a multimedia artist and during quarantine, Maddie collaged all of the wooden furniture in her apartment. He can also be found doing crossword puzzles at odd hours. * Corresponding authors. Maddie received her MS and BS in Biology from Brandeis University in 2021. Bartok O., Kyriacou C., Levine J., Sehgal A. and Kadener S. Adaptation of molecular circadian clockwork to environmental changes: a role for alternative splicing and miRNAs. Selected for Faculty of 1000 (Factor 3 Recommended). Contact the author . Understanding how circadian rhythms are generated, maintained, and adapted to changing conditions is key, as several diseases such as cancer and depression are associated with misalignment of the circadian clock with the environment. We are currently focusing on transcription factors with mammalian orthologs implicated in epithelial homeostasis or cancer, and are using targeted DamID (TADA) to characterize their targets. Stock center polar mechanism coordinates different regions of alternative splicing within a single sample... Jens did when he arrived in Boston DRSC-BTRR efforts is establishment of CRISPR pooled screening in cell lines from vectors... Found doing crossword puzzles at odd hours time by complex transcriptional and post-transcriptional feedback loops doing! 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