. Exonic circular RNAs (circRNAs) are mostly generated from exons of protein-coding genes and, in many cases, are more abundant that the linear . Moreover, we also showed that the neural and molecular circadian systems compensate and interact with each other. Ph.D. University of So Paulo (USP)- Brazil. Title. . 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. What are the general mechanism of the circadian clock to deal with genetic and/or environmental perturbations? What is their mechanisms of action? 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. Lerner I. Nogues G., Kadener S., Cramer P., Bentley D. and Kornblihtt A.R. Moreover, we also showed that the neural and molecular circadian systems compensate and interact with each other. Eric joined the Bandopadhayay Lab in 2020 where he is working to characterize driver mutations found in pediatric brain tumors and developing new approaches to treat these children with targeted therapies. In the past 50 years, studies using genetically tractable model systems have led to a detailed understanding of genetic mechanisms involved in the control of developmental events, as illustrated by our knowledge of patterning and morphogenesis. Anna developed a fascination for cancer biology while working towards her bachelors degree at Lund University, Sweden. Statuses. Selected for Faculty of 1000 (Factor 3 Recommended). Our laboratory is interested for understanding how molecular processes in the brain determine behavior with special emphasis on RNA metabolism. @skadener. We continue to evaluate and create new methods for genome engineering. Rosi is attending the structural MS workshop in Finland. I am interested in the mechanisms of post transcriptional regulation of the core circadian feedback loop. M.Sc., The University of Buenos Aires, Buenos Aires, Argentina Ph.D., The University of Buenos Aires, Buenos Aires, Argentina. Genome-Wide Analysis of Light- and Temperature-Entrained . Transcriptional activators differ in their abilities to control alternative splicing. In mature animals, cells and organs interact to maintain homeostasis and coordinate their physiological roles. In addition and most importantly, genome-wide libraries of transgenic RNAi lines are available that allow knockdown of any Drosophila gene in an organ or tissue-specific manner. 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. The work is a collaboration between Dr. Kadener's lab and Prof. Nikolaus Rajewsky from the Max Dellbruck Institute, Berlin, Germany. Now the stage is set for the most exciting questions, which we are currently working in the lab, by combining molecular, computational and RNA biology with advances techniques in genetics and neurosciences. In addition, these gRNA fly stock resources can be used for genome engineering of the promoter or coding regions. Sebastian Kadener. I am studying potential applications of the CRISPR/Cas13 system. A slow RNA polymerase II affects alternative splicing in vivo. Eric received his MS in biomedicine from Uppsala University, Sweden in 2010. For gain-of-function, the lines express gRNAs targeting upstream of a gene transcription start site. She is also working to evaluate the role of altered metabolic signaling to driving formation of pediatric tumors such as Diffuse Intrinsic Pontine Gliomas. 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. Alexander M. van der Linden, Matthew Beverly, Sebastian Kadener, Joseph Rodriguez, Sara Wasserman, Michael Rosbash, Piali Sengupta. and Kornblihtt A.R. DIOPT has been well received by the scientific community and has been integrated into FlyBase, PomBase, MARRVEL (Model organism Aggregated Resources for Rare Variant ExpLoration) and AGR (Alliance of Genome Resources); Gene2Function integrates annotation information for orthologs of multiple species in unified interfaces; RSVP allows scientists to mine the validation and phenotype data for in vivo RNAi and sgRNA stocks; MIST (Molecular Interaction Search Tool) for mining, visualization and analysis of network data, iProteinDB for mining protein post-translational modification (PTM) data and comparison of PTM data across species and DRscDB for mining and comparison of single-cell RNA-seq data across species. Clonally stable VK allelic choice instructs IgK repertoire. Bartok O., Teesalu M., Pandey V., Hanan M., Poukkula M., Havula E., Moussaieff A., Vodala S., Nahmias Y., Kadener S.* and Hietakangas V.* Cabut-dependent repressive branch of the sugar sensing transcriptional network regulates glyceroneogenesis. Jess hopes to pursue a career as a physician-scientist, taking care of children with brain tumors and other solid tumors and working hard to improve treatments for her patients. Elife 8. 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. Circadian clocks are remarkably robust: they are able to keep time without timing cues and are resilient to large variations in environmental conditions. Fededa J.P., Petrillo E., Gelfand M.S., Neverov A.D., Kadener S., Nogues G., Pelisch F., Baralle F.E., Muro A.F. PERIOD1-associated proteins modulate the negative limb of the mammalian circadian oscillator. 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. Circadian clocks are also exceptionallyplasticas they can quickly and specifically adjust to specific environmental cues. 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. B.S., University of Barcelona, Spain Ph.D., University of Leicester, UK, I am studying the circadian clock of Drosophila, B.S. As miR-183, the human ortholog of miR-263a, also regulates ENaC, our findings suggest miR-183 might be used as a treatment for CF. Media. 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. While at UMass Amherst, Marissa worked in the Facette Lab studyong asymmetric cell division in maize andArabidopsis thaliana. Among the next significant questions to address are how complex phenotypes arise in the context of the whole organism and how the programs regulating these phenotypes are influenced by genetic background and environment. 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. Zaffagni M, Kadener S. NEAT1 is overexpressed in Parkinson's disease substantia nigra and confers drug-inducible neuroprotection from oxidative stress. leptin), neural development, and behavior are conserved. This dual reporter can be used in either fixed or live tissues to monitor spatio-temporal activity of signaling pathways at an unprecedented resolution. Mouse-olfactory bulb, brain stem, and thalamus-Mock. She also loves sleeping in, making guacamole, and reading about art history. Its very important for us! 1 / 3 Looking for Postdoctoral researchers At the lab, I research the role of temperature in the synchronization of the Drosophila circadian clock. 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. He can also be found doing crossword puzzles at odd hours. Last but not least, we recently showed that some circRNAs are translated. Riley is currently working to understand genetic and epigenetic mechanisms of resistance in brain tumors, focusing on resistance to BET-bromodomain inhibitors and vulnerabilities induced by loss of mismatch repair proteins. Over the years, we have added a number of screening reagents and developed bioinformatics tools to improve the platform. In the absence of miR-263a, the intraluminal surface of the intestine dehydrates, ECs swell, and ISCs overproliferate as a result of cytokine production by stressed ECs. She received her BA in Molecular and Cell Biology from the University of California, Berkeley in 2019. 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. Stelzer Y., Bar S., Bartok O., Afik S., Ronen D., Kadener S.* and Benvenisty N.* Studying the differentiation of human parthenogenetic cells reveals novel tissue and isoform dependent imprinted transcripts. Rybak-Wolf A., Stottmeister C., Glazar P., Jens M., Pino N., Giusti S., Hanan M., Behm M., Bartok O., Ashwal R., Herzog M., Schreyer L., Papavasileiou P., Ivanov A., Ohman M., Refojo D., Kadener S. and Rajewsky N. Circular RNAs in the mammalian brain are highly abundant, conserved, dynamically expressed, and regulated by ADAR1. For example, the vertebrate CNS receives information regarding the status of peripheral metabolic processes via hormonal signaling and direct macromolecular sensing. Selected for Faculty of 1000 (Factor 3 Recommended). Jazmin is currently investigating how circRNA levels change at synapses and whether they are modulated by neuronal activity. 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. We showed that miRNAs have a key role in providing robustness to the circadian system both during development and in adults. de la Mata M., Alonso C.R., Kadener S., Fededa J.P., Blaustein M., Pelisch F., Cramer P., Bentley D. and Kornblihtt A.R. Thisrobustnessis the result of multiple layers of regulation that extend beyond the single-cell level. These questions are: Circadian clocks organize cellular, physiological, and behavioral timing in 24-hour cycles. Maddie received her MS and BS in Biology from Brandeis University in 2021. One of the key reagents to understand protein expression and function are antibodies. 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. *, Eliaz D.*, Cohen Chalamish S., Tschudi C., Unger R., Hashem Y., Kadener S. and Michaeli S. Pseudouridylation in. 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. Cs. Ultimately, the knowledge gained from these studies will generate testable hypotheses related to disease states such as diabetes, aging, and cancer, i.e., how biological processes observed in one tissue/organ (e.g., decreased cellular metabolism, mitochondrial dysfunction) may influence processes observed in a different tissue/organ. Pandey V., Turm H., Bekenstein U., Shifman S. and Kadener S. A new. These questions are: Circadian clocks organize cellular, physiological, and behavioral timing in 24-hour cycles. * Corresponding authors. Kadener, Sebastian / Brandeis University Publications. Ashwal-Fluss R., Meyer M., Pamudurti N.R., Ivanov A., Bartok O., Evantal N., Hanan M., Memczak S., Rajewsky N.* and Kadener S.* CircRNA biogenesis and canonical splicing compete with each other. leptin), neural development, and behavior are conserved, . We have taken a number of approaches to address the spatial and temporal regulation of signaling pathway activities in the gut epithelium. 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). at USC we have extended this approach to the mouse. Mezan S., Feuz JD, Deplancke B. and Kadener S. PDF signaling is an integral part of the. What are the general mechanism of the circadian clock to deal with genetic and/or environmental perturbations? 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. Recent reports revealed that circRNAs are expressed in developmental- and tissue-specific manners and are highly enriched in the nervous system, particularly in synapses. In the Bando Lab, Adam is studying how alterations in chromatin factors lead to pediatric gliomagenesis with the ultimate goal of discovering novel therapeutic approaches. 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. Selected for Faculty of 1000 (Factor 9 Exceptional). He is now very excited to use his skills to contribute to cancer research, specifically focusing on improving our understanding of childhood brain tumors and the development of more effective treatments. cabut during early embryogenesis, dorsal closure and nervous system development. Determine the nature of circadian rhythms within organisms. A polar mechanism coordinates different regions of alternative splicing within a single gene. *, Bartok O. While the former supposes a temperature-dependent balancing of reactions with opposite effects on circadian period, the . Metazoan MicroRNAs (2018) David P. Bartel CELL Non-canonical functions of microRNA pathway enzymes - Drosha, DGCR8, Dicer and Ago proteins Clonally stable VK allelic choice instructs IgK repertoire. Selected for Faculty of 1000 (Factor 3 Recommended). Informative set of videos on insect physiology and endocrinology: New paper: Hanan M, Simchovitz A, Yayon N, Vaknine S, Cohen-Fultheim R, Karmon M, Madrer N, Rohrlich TM, Maman M, Bennett ER, Greenberg DS, Meshorer E, Levanon EY, Soreq H, Kadener S. Past, present, and future of circRNAs. Nov, 2017. Regulation of alternative splicing by a transcriptional enhancer through RNA pol II elongation. Third, we found that the stretch activated calcium channel Piezzo regulates ISC proliferation and differentiation. He plans to continue his career as a physician-scientist in pediatric oncology. Allada R., Kadener S., Nandakumar N. and Rosbash M. A recessive mutant of, Portal D., Espinosa J.M., Lobo G.S., Kadener S., Pereira C.A., de la Mata M., Tang Z., Lin R.J., Kornblihtt A.R., Baralle F.E., Flawia M.M. Wittenbrink N, Ananthasubramaniam B, Mnch M, Koller B, Maier B, Weschke C, Bes F, de Zeeuw J, Nowozin C, Wahnschaffe A, Wisniewski S, Zaleska M, Bartok O, Ashwal-Fluss R, Lammert H, Herzel H, Hummel M, Kadener S, Kunz D, Kramer A. Levin-Klein R., Fraenkel S., Lichtenstein M., Matheson L., Bartok O., Nevo Y., Kadener S., Corcoran A., Cedar H., Bergman Y. Nogues G., Kadener S., Cramer P., Bentley D. and Kornblihtt A.R. Olivia worked in two labs during her time at WashU: Dr. Natalie Muellers paleoethnobotany lab where she analyzed plant samples from Late Archaic food sites in modern-day Mississippi, and Dr. Crickette Sanzs Digital Lab for Primatology where she studied captive and wild chimpanzee ecology and ontogeny. 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. *, Afik S., Menet J., Wolfson V., Weissbein U., Haimovich D., Gafni C., Friedman N., Rosbash M. and Kadener S. . Verified email at brandeis.edu - Homepage. Protocol. Molecular Neurobiology and RNA Metabolism Laboratory. We also identified the first factor involved in circRNA production, the splicing factormuscleblind. Cohen-Hadad Y., Altarescu G., Eldar-Geva T., Levi-Lahad E., Zhang M., Rogaeva, E. Gotkine M., Bartok O., Ashwal-Fluss R., Kadener S., Epsztejn-Litman S., Eiges R. Marked differences in C9orf72 methylation status and isoform expression between C9/ALS human embryonic and induced pluripotent stem cells. Supposes a temperature-dependent balancing of reactions with opposite effects on circadian period, the lines express gRNAs targeting upstream a. 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