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Antje Janosch, Carolin Kaffka, Marc Bickle
Unbiased Phenotype Detection Using Negative Controls
Pending, 1-1 (2018)
Supplementary Website  

@article{Janosch7217,
author={Antje Janosch, Carolin Kaffka, Marc Bickle},
title={Unbiased Phenotype Detection Using Negative Controls},
journal ={Pending},
volume={},
pages={1--1},
year=2018
}

Juliana Roscito, Katrin Sameith, Genis Parra, Bjoern Langer, Andreas Petzold, Claudia Moebius, Marc Bickle, Miguel Trefaut Rodrigues, Michael Hiller
Phenotype loss is associated with widespread divergence of the gene regulatory landscape in evolution.
Nat Commun, 9(1) 4737-4737 (2018)
  PubMed Source   

Detecting the genomic changes underlying phenotypic changes between species is a main goal of evolutionary biology and genomics. Evolutionary theory predicts that changes in cis-regulatory elements are important for morphological changes. We combined genome sequencing, functional genomics and genome-wide comparative analyses to investigate regulatory elements in lineages that lost morphological traits. We first show that limb loss in snakes is associated with widespread divergence of limb regulatory elements. We next show that eye degeneration in subterranean mammals is associated with widespread divergence of eye regulatory elements. In both cases, sequence divergence results in an extensive loss of transcription factor binding sites. Importantly, diverged regulatory elements are associated with genes required for normal limb patterning or normal eye development and function, suggesting that regulatory divergence contributed to the loss of these phenotypes. Together, our results show that genome-wide decay of the phenotype-specific cis-regulatory landscape is a hallmark of lost morphological traits.
@article{Roscito7256,
author={Juliana Roscito, Katrin Sameith, Genis Parra, Bjoern Langer, Andreas Petzold, Claudia Moebius, Marc Bickle, Miguel Trefaut Rodrigues, Michael Hiller},
title={Phenotype loss is associated with widespread divergence of the gene regulatory landscape in evolution.},
journal ={Nature communications},
volume={9},
issue ={1},
pages={4737--4737},
year=2018
}

Virag Sharma, Michael Hiller
Loss of enzymes in the bile acid synthesis pathway explains differences in bile composition among mammals.
Genome Biol Evol, 1-1 (2018)
PubMed Source   

Bile acids are important for absorbing nutrients. Most mammals produce cholic and chenodeoxycholic bile acids. Here, we investigated genes in the bile acid synthesis pathway in four mammals that deviate from the usual mammalian bile composition. First, we show that naked-mole rats, elephants, and manatees repeatedly inactivated CYP8B1, an enzyme uniquely required for cholic acid synthesis, which explains the absence of cholic acid in these species. Second, no gene-inactivating mutations were found in any pathway gene in the rhinoceros, a species that lacks bile acids, indicating an evolutionarily-recent change in its bile composition. Third, elephants and/or manatees that also lack bile acids altogether have lost additional non-essential enzymes (SLC27A5, ACOX2). Apart from uncovering genomic differences explaining deviations in bile composition, our analysis of bile acid enzymes in bile acid-lacking species suggests that essentiality prevents gene loss, while loss of pleiotropic genes is permitted if their other functions are compensated by functionally-related proteins.
@article{Sharma7254,
author={Virag Sharma, Michael Hiller},
title={Loss of enzymes in the bile acid synthesis pathway explains differences in bile composition among mammals.},
journal ={Genome biology and evolution},
volume={},
pages={1--1},
year=2018
}

Olga Vvedenskaya, Yuting Wang, Jacobo Miranda Ackerman, Oskar Knittelfelder, Andrej Shevchenko
Analytical challenges in human plasma lipidomics: A winding path towards the truth
Trends Analyt Chem, 1-1 (2018)
Source   

Human plasma lipidome has been extensively studied in many pathophysiological contexts with the hope of identifying biomarkers for early diagnostics and monitoring the progression and treatment of a broad spectrum of diseases. However, despite remarkable progress in lipidomics technologies, the concordance of lipidomics measurements between independent laboratories remains limited and not fulfilling the criteria of common laboratory diagnostics. Here we highlighted a few critical aspects of epidemiological studies of the plasma lipidome, including the selection of study cohorts, collection of plasma samples as well as extraction, identification and quantification of lipids. We argue that reporting the abundances of plasma lipids as molar concentrations is a key turning point during the transition of research lipidomics into a common tool of clinical diagnostics.
@article{Vvedenskaya7251,
author={Olga Vvedenskaya, Yuting Wang, Jacobo Miranda Ackerman, Oskar Knittelfelder, Andrej Shevchenko},
title={Analytical challenges in human plasma lipidomics: A winding path towards the truth},
journal ={Trends in analytical chemistry},
volume={},
pages={1--1},
year=2018
}

Samir Vaid, J Gray Camp, Lena Hersemann, Christina Eugster Oegema, Anne-Kristin Heninger, Sylke Winkler, Holger Brandl, Mihail Sarov, Barbara Treutlein, Wieland Huttner, Takashi Namba
A novel population of Hopx-dependent basal radial glial cells in the developing mouse neocortex.
Development, 145(20) Art. No. doi: 10.1242/dev.169276 (2018)
PubMed Source   

A specific subpopulation of neural progenitor cells, the basal radial glial cells (bRGCs) of the outer subventricular zone (OSVZ), are thought to have a key role in the evolutionary expansion of the mammalian neocortex. In the developing lissencephalic mouse neocortex, bRGCs exist at low abundance and show significant molecular differences from bRGCs in developing gyrencephalic species. Here, we demonstrate that the developing mouse medial neocortex (medNcx), in contrast to the canonically studied lateral neocortex (latNcx), exhibits an OSVZ and an abundance of bRGCs similar to that in developing gyrencephalic neocortex. Unlike bRGCs in developing mouse latNcx, the bRGCs in medNcx exhibit human bRGC-like gene expression, including expression of Hopx, a human bRGC marker. Disruption of Hopx expression in mouse embryonic medNcx and forced Hopx expression in mouse embryonic latNcx demonstrate that Hopx is required and sufficient, respectively, for bRGC abundance as found in the developing gyrencephalic neocortex. Taken together, our data identify a novel bRGC subpopulation in developing mouse medNcx that is highly related to bRGCs of developing gyrencephalic neocortex.
@article{Vaid7234,
author={Samir Vaid, J Gray Camp, Lena Hersemann, Christina Eugster Oegema, Anne-Kristin Heninger, Sylke Winkler, Holger Brandl, Mihail Sarov, Barbara Treutlein, Wieland Huttner, Takashi Namba},
title={A novel population of Hopx-dependent basal radial glial cells in the developing mouse neocortex.},
journal ={Development (Cambridge, England)},
volume={145},
issue ={20},
pages={null--null},
year=2018
}

David Jebb, Michael Hiller
Recurrent loss of HMGCS2 shows that ketogenesis is not essential for the evolution of large mammalian brains.
Elife, 7 Art. No. e38906 (2018)
  PubMed Source   

Apart from glucose, fatty acid-derived ketone bodies provide metabolic energy for the brain during fasting and neonatal development. We investigated the evolution of HMGCS2, the key enzyme required for ketone body biosynthesis (ketogenesis). Unexpectedly, we found that three mammalian lineages, comprising cetaceans (dolphins and whales), elephants and mastodons, and Old World fruit bats have lost this gene. Remarkably, many of these species have exceptionally large brains and signs of intelligent behavior. While fruit bats are sensitive to starvation, cetaceans and elephants can still withstand periods of fasting. This suggests that alternative strategies to fuel large brains during fasting evolved repeatedly and reveals flexibility in mammalian energy metabolism. Furthermore, we show that HMGCS2 loss preceded brain size expansion in toothed whales and elephants. Thus, while ketogenesis was likely important for brain size expansion in modern humans, ketogenesis is not a universal precondition for the evolution of large mammalian brains.
@article{Jebb7221,
author={David Jebb, Michael Hiller},
title={Recurrent loss of HMGCS2 shows that ketogenesis is not essential for the evolution of large mammalian brains.},
journal ={eLife},
volume={7},
pages={null--null},
year=2018
}

Till Korten, Elena Tavkin, Lara Scharrel, Vandana Singh Kushwaha, Stefan Diez
An automated in vitro motility assay for high-throughput studies of molecular motors.
Lab on a chip, 18(20) 3196-3206 (2018)
PubMed Source   

Molecular motors, essential to force-generation and cargo transport within cells, are invaluable tools for powering nanobiotechnological lab-on-a-chip devices. These devices are based on in vitro motility assays that reconstitute molecular transport with purified motor proteins, requiring a deep understanding of the biophysical properties of motor proteins and thorough optimization to enable motility under varying environmental conditions. Until now, these assays have been prepared manually, severely limiting throughput. To overcome this limitation, we developed an in vitro motility assay where sample preparation, imaging and data evaluation are fully automated, enabling the processing of a 384-well plate within less than three hours. We demonstrate the automated assay for the analysis of peptide inhibitors for kinesin-1 at a wide range of concentrations, revealing that the IAK domain responsible for kinesin-1 auto-inhibition is both necessary and sufficient to decrease the affinity of the motor protein for microtubules, an aspect that was hidden in previous experiments due to scarcity of data.
@article{Korten7240,
author={Till Korten, Elena Tavkin, Lara Scharrel, Vandana Singh Kushwaha, Stefan Diez},
title={An automated in vitro motility assay for high-throughput studies of molecular motors.},
journal ={Lab on a chip},
volume={18},
issue ={20},
pages={3196--3206},
year=2018
}

Petra Schwille, Joachim P. Spatz, Katharina Landfester, Eberhard Bodenschatz, Stephan Herminghaus, Victor Sourjik, Tobias Erb, Philippe Bastiaens, Reinhard Lipowsky, Anthony Hyman, Peter Dabrock, Jean-Christophe Baret, Tanja Vidakovic-Koch, Peter Bieling, Rumiana Dimova, Hannes Mutschler, Tom Robinson, T-Y Dora Tang, Seraphine Wegner, Kai Sundmacher
MaxSynBio: Avenues Towards Creating Cells from the Bottom Up.
Angew Chem Int Ed Engl, 57(41) 13382-13392 (2018)
PubMed Source   

A large German research consortium mainly within the Max Planck Society ("MaxSynBio") was formed to investigate living systems from a fundamental perspective. The research program of MaxSynBio relies solely on the bottom-up approach to synthetic biology. MaxSynBio focuses on the detailed analysis and understanding of essential processes of life through modular reconstitution in minimal synthetic systems. The ultimate goal is to construct a basic living unit entirely from non-living components. The fundamental insights gained from the activities in MaxSynBio could eventually be utilized for establishing a new generation of biotechnological processes, which would be based on synthetic cell constructs that replace the natural cells currently used in conventional biotechnology.
@article{Schwille7138,
author={Petra Schwille, Joachim P. Spatz, Katharina Landfester, Eberhard Bodenschatz, Stephan Herminghaus, Victor Sourjik, Tobias Erb, Philippe Bastiaens, Reinhard Lipowsky, Anthony Hyman, Peter Dabrock, Jean-Christophe Baret, Tanja Vidakovic-Koch, Peter Bieling, Rumiana Dimova, Hannes Mutschler, Tom Robinson, T-Y Dora Tang, Seraphine Wegner, Kai Sundmacher},
title={MaxSynBio: Avenues Towards Creating Cells from the Bottom Up.},
journal ={Angewandte Chemie (International ed. in English)},
volume={57},
issue ={41},
pages={13382--13392},
year=2018
}

Bo Burla, Makoto Arita, Makoto Arita, Anne K Bendt, Amaury Cazenave-Gassiot, Edward A Dennis, Kim Ekroos, Xianlin Han, Kazutaka Ikeda, Gerhard Liebisch, Michelle I Lin, Tze Ping Loh, Peter J Meikle, Matej Orešič, Oswald Quehenberger, Andrej Shevchenko, Federico Torta, Michael J O Wakelam, Craig E Wheelock, Markus R Wenk
MS-based lipidomics of human blood plasma: a community-initiated position paper to develop accepted guidelines.
J Lipid Res, 59(10) 2001-2017 (2018)
PubMed Source   

Human blood is a self-regenerating lipid-rich biological fluid that is routinely collected in hospital settings. The inventory of lipid molecules found in blood plasma (plasma lipidome) offers insights into individual metabolism and physiology in health and disease. Disturbances in the plasma lipidome also occur in conditions that are not directly linked to lipid metabolism; therefore, plasma lipidomics based on MS is an emerging tool in an array of clinical diagnostics and disease management. However, challenges exist in the translation of such lipidomic data to clinical applications. These relate to the reproducibility, accuracy, and precision of lipid quantitation, study design, sample handling, and data sharing. This position paper emerged from a workshop that initiated a community-led process to elaborate and define a set of generally accepted guidelines for quantitative MS-based lipidomics of blood plasma or serum, with harmonization of data acquired on different instrumentation platforms across independent laboratories as an ultimate goal. We hope that other fields may benefit from and follow such a precedent.
@article{Burla7205,
author={Bo Burla, Makoto Arita, Makoto Arita, Anne K Bendt, Amaury Cazenave-Gassiot, Edward A Dennis, Kim Ekroos, Xianlin Han, Kazutaka Ikeda, Gerhard Liebisch, Michelle I Lin, Tze Ping Loh, Peter J Meikle, Matej Orešič, Oswald Quehenberger, Andrej Shevchenko, Federico Torta, Michael J O Wakelam, Craig E Wheelock, Markus R Wenk},
title={MS-based lipidomics of human blood plasma: a community-initiated position paper to develop accepted guidelines.},
journal ={Journal of lipid research},
volume={59},
issue ={10},
pages={2001--2017},
year=2018
}

Yusuke Toyoda, Busra Akarlar, Mihail Sarov, Nurhan Ozlu, Shigeaki Saitoh
Extracellular glucose level regulates dependence on GRP78 for cell surface localization of multipass transmembrane proteins in HeLa cells.
FEBS Lett, 592(19) 3295-3304 (2018)
PubMed Source   

Many human-cultured cell lines survive glucose starvation, but the underlying mechanisms remain unclear. Here, we searched for proteins required for cellular adaptation to glucose-limited conditions and identified several endoplasmic reticulum chaperones in the glucose-regulated protein (GRP) family as proteins enriched in the cellular membrane. Surprisingly, these proteins, which are required for cell surface localization of GLUT1 under high-glucose conditions, become dispensable for targeting GLUT1 to the surface upon glucose starvation. In marked contrast, cell surface localization of single-pass transmembrane proteins, such as epidermal growth factor receptor and CD98, is not disturbed by GRP78 depletion regardless of the extracellular glucose level. These results indicate that the extracellular glucose level regulates dependence on the GRPs for cell surface localization of multipass transmembrane proteins.
@article{Toyoda7233,
author={Yusuke Toyoda, Busra Akarlar, Mihail Sarov, Nurhan Ozlu, Shigeaki Saitoh},
title={Extracellular glucose level regulates dependence on GRP78 for cell surface localization of multipass transmembrane proteins in HeLa cells.},
journal ={FEBS letters},
volume={592},
issue ={19},
pages={3295--3304},
year=2018
}