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collection => FelixNagel\GenericGallery\Domain\Model\GalleryCollectionprototypemodified object (5 items) 0000000000000ab00000000000000000 => FelixNagel\GenericGallery\Domain\Model\GalleryItemprototypepersistent entity (uid=27, pid=56624) ttContentUid => protected273289 (integer) title => protected'Modeling the immune regulation of clonal hematopoiesis' (54 chars) link => protected't3://page?uid=56935' (19 chars) imageReference => protectedTYPO3\CMS\Extbase\Domain\Model\FileReferenceprototypepersistent entity (uid=157081, pid=56624) uidLocal => protected345665 (integer) originalResource => protectedNULL uid => protected157081 (integer) _localizedUid => protected157081 (integer)modified _languageUid => protected0 (integer)modified _versionedUid => protected157081 (integer)modified pid => protected56624 (integer) image => protectedNULL textItems => protectedTYPO3\CMS\Extbase\Persistence\ObjectStorageprototypeobject (3 items) 0000000000000a460000000000000000 => FelixNagel\GenericGallery\Domain\Model\TextItemprototypepersistent entity (uid=14, pid=56624) bodytext => protected'<p>Supervisor:&nbsp;<a href="https://www.helmholtz-munich.de/en/aih/pi/carst
                  en-marr" target="_blank">Dr. Carsten Marr</a><br /> Group:&nbsp;<a href="htt
                  ps://www.helmholtz-munich.de/en/aih/research-groups/marr-group" target="_bla
                  nk">Marr Group</a><br /> Institute:&nbsp;<a href="https://www.helmholtz-muni
                  ch.de/en/aih" target="_blank">Institute of AI for Health</a>, Helmholtz Muni
                  ch</p> <p>Collaborating Supervisor: Dr. Linus Schumacher<br /> Group:&nbsp;
                  <a href="https://www.ed.ac.uk/regenerative-medicine/research/linus-schumache
                  r" target="_blank">Linus Schumacher Group</a><br /> Institute: University of
                   Edinburgh, Centre for Regenerative Medicine</p>
' (656 chars) position => protected'0,0' (3 chars) width => protected'0' (1 chars) uid => protected14 (integer) _localizedUid => protected14 (integer)modified _languageUid => protectedNULL _versionedUid => protected14 (integer)modified pid => protected56624 (integer)
0000000000000a1c0000000000000000 => FelixNagel\GenericGallery\Domain\Model\TextItemprototypepersistent entity (uid=15, pid=56624) bodytext => protected'<p>Project Description:</p> <p>Akute leukemia is a blood cancer that usuall
                  y starts displaying symptoms in a late stage, making its treatment difficult
                   and often unsuccessful. The disease is caused by carcinogenic mutations in
                  hematopoietic stem cells (HSCs). They cause the cells to proliferate instead
                   of differentiating further towards mature blood cells. Recently, it has bee
                  n observed that certain mutations are present in patients already a few deca
                  des before the onset of leukemia, a property called clonal hematopoiesis of
                  indeterminate potential (CHIP) [1,2].</p> <p><br /> In the Marr Lab at Helm
                  holtz Munich&nbsp;and at the Schumacher lab at the University of Edinburgh,
                  we work on understanding hematopoiesis [3,4], the kinetics of CHIP [5], and
                  the role of the immune system in the regulation of the CHIP mutated single c
                  ells. This could help us prevent the development of leukemia, or lead to the
                   development of less invasive treatments than chemotherapy and bone marrow t
                  ransplantation.<br /> In the PhD project, the student will address the quest
                  ion of how the immune system deals with CHIP from two different perspectives
                  , using contemporary analytical tools. The first level will involve mathemat
                  ical modeling of the kinetics of CHIP mutations and the blood production sys
                  tem. The goal here is to use data from large cohorts to find phenotypic evid
                  ence and properties of the immune system activity. This will include stochas
                  tic modeling, ordinary differential equations and statistical inference to d
                  escribe hematopoiesis. The second level will be understanding the molecular
                  and epigenetic mechanisms of immune regulation of CHIP. The candidate will a
                  nalyze data from blood and bone marrow smears, single cell RNA sequencing, s
                  ingle cell ATAC sequencing, chromatin immunoprecipitation, and mass spectros
                  copy with bioinformatic techniques and machine learnin models to understand
                  the signaling pathways between CHIP cells and immune cells. The student will
                   enter a 4 year program ...
' (2691 chars) position => protected'0,0' (3 chars) width => protected'0' (1 chars) uid => protected15 (integer) _localizedUid => protected15 (integer)modified _languageUid => protectedNULL _versionedUid => protected15 (integer)modified pid => protected56624 (integer)
0000000000000a960000000000000000 => FelixNagel\GenericGallery\Domain\Model\TextItemprototypepersistent entity (uid=16, pid=56624) bodytext => protected'<p>Relevant Literature:</p> <ul> <li>Genovese G, Kähler AK, Handsaker RE,
                   Lindberg J, Rose SA, Bakhoum SF, et al. Clonal hematopoiesis and blood-canc
                  er risk inferred from blood DNA sequence. N Engl J Med. 2014;371: 2477–248
                  7</li> <li>Jaiswal S, Fontanillas P, Flannick J, Manning A, Grauman PV, Mar
                   BG, et al. Age-related clonal hematopoiesis associated with adverse outcome
                  s. N Engl J Med. 2014;371: 2488–2498</li> <li>Bast L, Buck MC, Hecker JS,
                   Oostendorp RAJ, Götze KS, Marr C. Computational modeling of stem and proge
                  nitor cell kinetics identifies plausible hematopoietic lineage hierarchies.
                  iScience. 2021;24: 102120</li> <li>Buggenthin F, Buettner F, Hoppe PS, Ende
                  le M, Kroiss M, Strasser M, et al. Prospective identification of hematopoiet
                  ic lineage choice by deep learning. Nat Methods. 2017;14: 403–406</li> <l
                  i>Robertson NA, Latorre-Crespo E, Terradas-Terradas M, Lemos-Portela J, Purc
                  ell AC, Livesey BJ, et al. Longitudinal dynamics of clonal hematopoiesis ide
                  ntifies gene-specific fitness effects. Nat Med. 2022;28: 1439–1446</li> </
                  ul>
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0000000000000a330000000000000000 => FelixNagel\GenericGallery\Domain\Model\GalleryItemprototypepersistent entity (uid=28, pid=56624) ttContentUid => protected273289 (integer) title => protected'Single-cell multiomic analysis of transposable elements with new Bayesian ma
            chine learning methods
' (98 chars) link => protected't3://page?uid=56934' (19 chars) imageReference => protectedTYPO3\CMS\Extbase\Domain\Model\FileReferenceprototypepersistent entity (uid=157082, pid=56624) uidLocal => protected345666 (integer) originalResource => protectedNULL uid => protected157082 (integer) _localizedUid => protected157082 (integer)modified _languageUid => protected0 (integer)modified _versionedUid => protected157082 (integer)modified pid => protected56624 (integer) image => protectedNULL textItems => protectedTYPO3\CMS\Extbase\Persistence\ObjectStorageprototypeobject (3 items) 0000000000000a3e0000000000000000 => FelixNagel\GenericGallery\Domain\Model\TextItemprototypepersistent entity (uid=17, pid=56624) bodytext => protected'<p>Main Supervisor: Dr. Antonio Scialdone<br /> Group:&nbsp;<a href="https:/
                  /www.helmholtz-munich.de/en/ies/research-groups/scialdone-lab" target="_blan
                  k">Physics and Data-Based Modelling of Cellular Identity Changes</a><br /> I
                  nstitute:&nbsp;<a href="https://www.helmholtz-munich.de/en/ies" target="_bla
                  nk">Institute of Epigenetics and Stem Cells</a>, Helmholtz Center Munich</p>
                   <p>Collaborating Supervisor: Dr. Catalina Vallejos<br /> Group:&nbsp;<a hr
                  ef="https://www.ed.ac.uk/mrc-human-genetics-unit/research/vallejos-group" ta
                  rget="_blank">Biomedical Data Science</a><br /> Institute: MRC Human Genetic
                  s Unit, Institute of Genetics &amp; Molecular Medicine, University of Edinbu
                  rgh</p>
' (691 chars) position => protected'0,0' (3 chars) width => protected'0' (1 chars) uid => protected17 (integer) _localizedUid => protected17 (integer)modified _languageUid => protectedNULL _versionedUid => protected17 (integer)modified pid => protected56624 (integer)
0000000000000a1b0000000000000000 => FelixNagel\GenericGallery\Domain\Model\TextItemprototypepersistent entity (uid=18, pid=56624) bodytext => protected'<p>Project Description:</p> <p>Transposable elements (TEs) are mobile DNA s
                  equences that constitute large fractions of many eukaryotic genomes. They ha
                  ve an increasingly recognized role in regulating cellular identity changes i
                  n many different contexts, like embryonic development and the onset of many
                  diseases, including neurodegenerative diseases and cancer (Bourque et al. 20
                  18). However, we still know little about how they are regulated. The current
                   availability of a large number of single-cell omic datasets provides a grea
                  t opportunity to map the transcriptional activity and the chromatin state of
                   these elements at a single-cell resolution genome-wide. However, there are
                  fundamental computational challenges that remain to be solved. The main chal
                  lenge comes from the repetitive nature of TEs, which hinders the mapping of
                  reads originating from them. The currently available computational tools des
                  igned to address this challenge either profile TEs at a sub-family level, lo
                  sing any information on the TE genomic location; or exploit mutations to pin
                  point the location of TEs, a strategy that fails with “young” intact TEs
                   having a low substitution rate.</p> <p><br /> This project has two main ai
                  ms: (i) devise new computational methods to characterize the transcriptional
                   and chromatin state of TEs from single-cell sequencing datasets; (ii) use t
                  hese methods to characterize TEs regulation during human embryonic developme
                  nt and in stem-cell-based models of human embryos.</p> <p><br /> For the fi
                  rst aim, we will develop a novel algorithm based on Bayesian Machine Learnin
                  g starting from existing approaches to analyze single-cell RNA-seq datasets
                  (Eling et al. 2018), which will be extended to explicitly model ambiguous re
                  ads in scRNA-seq data as well as other types of sequencing data, like single
                  -cell ATAC-seq and bisulfite sequencing (Kapourani et al. 2021). This will e
                  nable us to also analyze single-cell multi-omic datasets and investigate the
                   regulation of TEs in va...
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0000000000001e3b0000000000000000 => FelixNagel\GenericGallery\Domain\Model\TextItemprototypepersistent entity (uid=19, pid=56624) bodytext => protected'<p>Relevant Literature:</p> <ul> <li>Bourque, Guillaume, Kathleen H. Burns
                  , Mary Gehring, Vera Gorbunova, Andrei Seluanov, Molly Hammell, Michaël Imb
                  eault, et al. 2018. “Ten Things You Should Know about Transposable Element
                  s.” Genome Biology 19 (1): 199</li> <li>Eling, Nils, Arianne C. Richard,
                  Sylvia Richardson, John C. Marioni, and Catalina A. Vallejos. 2018. “Corre
                  cting the Mean-Variance Dependency for Differential Variability Testing Usin
                  g Single-Cell RNA Sequencing Data.” Cell Systems 7 (3): 284–94.e12</li>
                   <li>Kapourani, Chantriolnt-Andreas, Ricard Argelaguet, Guido Sanguinetti, a
                  nd Catalina A. Vallejos. 2021. “scMET: Bayesian Modeling of DNA Methylatio
                  n Heterogeneity at Single-Cell Resolution.” Genome Biology 22 (1): 114</li
                  > <li>Scialdone, Antonio, and Nicolas Rivron. 2022. “In Preprints: Improv
                  ing and Interrogating Embryo Models.” Development 149 (23).&nbsp;<a href="
                  https://doi.org/10.1242/dev.201404" target="_blank">doi.org/10.1242/dev.2014
                  04</a></li> <li>Tyser, Richard C. V., Elmir Mahammadov, Shota Nakanoh, Ludo
                  vic Vallier, Antonio Scialdone, and Shankar Srinivas. 2021. “Single-Cell T
                  ranscriptomic Characterization of a Gastrulating Human Embryo.” Nature 600
                   (November): 285</li> </ul>
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0000000000000a440000000000000000 => FelixNagel\GenericGallery\Domain\Model\GalleryItemprototypepersistent entity (uid=29, pid=56624) ttContentUid => protected273289 (integer) title => protected'Single cell epigenomic study of the frequency, dynamics and origin of resist
            ant epimutations in response to external insults
' (124 chars) link => protected't3://page?uid=56936' (19 chars) imageReference => protectedTYPO3\CMS\Extbase\Domain\Model\FileReferenceprototypepersistent entity (uid=157083, pid=56624) uidLocal => protected345667 (integer) originalResource => protectedNULL uid => protected157083 (integer) _localizedUid => protected157083 (integer)modified _languageUid => protected0 (integer)modified _versionedUid => protected157083 (integer)modified pid => protected56624 (integer) image => protectedNULL textItems => protectedTYPO3\CMS\Extbase\Persistence\ObjectStorageprototypeobject (3 items) 0000000000000a370000000000000000 => FelixNagel\GenericGallery\Domain\Model\TextItemprototypepersistent entity (uid=21, pid=56624) bodytext => protected'<p>Main Supervisor: Dr. Maria Colomé-Tatché<br /> Group:&nbsp;<a href="htt
                  ps://www.helmholtz-munich.de/en/icb/research-groups/colome-tatche-lab" targe
                  t="_blank">Computational Epigenomics</a><br /> Institute:&nbsp;<a href="http
                  s://www.helmholtz-munich.de/en/computational-health-center" target="_blank">
                  Institute of Computational Biology</a>, Helmholtz Center Munich</p> <p>Co
                  llaborating Supervisor: Dr. Robin Allshire<br /> Group:&nbsp;<a href="https:
                  //www.wcb.ed.ac.uk/research/allshire" target="_blank">Wellcome Centre for Ce
                  ll Biology</a><br /> Institute:&nbsp; Institute of Cell Biology, School of B
                  iological Sciences, University of Edinburgh</p>
' (655 chars) position => protected'0,0' (3 chars) width => protected'0' (1 chars) uid => protected21 (integer) _localizedUid => protected21 (integer)modified _languageUid => protectedNULL _versionedUid => protected21 (integer)modified pid => protected56624 (integer)
0000000000000a140000000000000000 => FelixNagel\GenericGallery\Domain\Model\TextItemprototypepersistent entity (uid=22, pid=56624) bodytext => protected'<p>Project Description:</p> <p>Fungal survival in harsh environments involv
                  es stress-sensing pathways that reprogram their proteomes. New conditions, i
                  ncluding climate change, can push opportunistic fungi to colonise novel nich
                  es, potentially becoming harmful pathogens. Effective antifungal/fungicide t
                  reatments are limited in number precisely because fungi are adept at resisti
                  ng challenges. Antifungal resistance is increasingly prevalent, raising fung
                  al-borne disease frequencies in humans and crops1. Conventional wisdom that
                  resistance results solely from genetic mutations was overturned by our disco
                  very that external insults selects for cells with a distinct epigenetic land
                  scape - repressive heterochromatin over various genes whose reduced expressi
                  on confers resistance (e.g. mitochondrial proteins)2,3. Such heterochromatin
                  -dependent ‘epimutations’ are unstable, slowly losing resistance upon ex
                  ternal insult removal. We hypothesize that extracellular stresses, including
                   fungicides widely used in agriculture, reprogramme fungal epigenomes so tha
                  t they transiently acquire heterochromatin at locations which confer heritab
                  le, but unstable, resistance. By employing single cell analysis of lineages
                  seeded by just one cell we aim to provide insight into the mechanisms utiliz
                  ed by cells to mediate epimutant-mediated resistance. This project will comb
                  ine the power of classic Luria-Delbruck fluctuation tests with low cell numb
                  er/single cell (ATAC-seq, Cut&amp;Tag and RNA-seq) sequencing workflows to d
                  issect the events that result in the emergence of transiently antifungal/fun
                  gicide resistant lineages due to epimutation formation.</p>
' (1655 chars) position => protected'0,0' (3 chars) width => protected'0' (1 chars) uid => protected22 (integer) _localizedUid => protected22 (integer)modified _languageUid => protectedNULL _versionedUid => protected22 (integer)modified pid => protected56624 (integer)
00000000000009ed0000000000000000 => FelixNagel\GenericGallery\Domain\Model\TextItemprototypepersistent entity (uid=23, pid=56624) bodytext => protected'<p>Relevant Literature:</p> <ul> <li>Fisher MC, Hawkins NJ, Sanglard D. &a
                  mp; Gurr SJ. (2018) Worldwide emergence of resistance to antifungal drugs ch
                  allenges human health and food security. Science 360, 739–742</li> <li>To
                  rres-Garcia S, Yaseen I, Shukla M, Audergon PNCB, White SA, Pidoux AL, Allsh
                  ire RC. (2020). Epigenetic gene silencing by heterochromatin primes fungal r
                  esistance. Nature 585, 453–458</li> <li>Yaseen I, White SA, Torres-Garcia
                   S, Spanos C, Lafos M, Gaberdiel E, Yeboah R, El Karoui M, Rappsilber J, Pid
                  oux AL, Allshire RC. (2022) Proteasome-dependent truncation of the negative
                  heterochromatin regulator Epe1 mediates antifungal resistance. Nature Struct
                  ure &amp; Molecular Biology (in press); BioRXiv:&nbsp;<a href="https://doi.o
                  rg/10.1101/2021.12.20.473483" target="_blank">doi.org/10.1101/2021.12.20.473
                  483</a></li> <li>A. Danese, M.L. Richter, D.S. Fischer, F.J. Theis and M. C
                  olomé-Tatché. EpiScanpy: integrated single-cell epigenomic analysis. Nat.
                  Commun. 12, 5228 (2021).</li> <li>A. vd Graaf, R. Wardenaar, D.A. Neumann,
                  A. Taudt, R.G. Shaw, R.C. Jansen, R.J. Schmitz*, M. Colomé-Tatché*, F. Joh
                  annes*. Rate, spectrum and evolutionary dynamics of spontaneous epimutations
                  . Proc. Natl. Acad. Sci. USA 112:6676-81 (2015). (* cocorresponding authors)
                  </li> </ul>
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0000000000001e3a0000000000000000 => FelixNagel\GenericGallery\Domain\Model\GalleryItemprototypepersistent entity (uid=30, pid=56624) ttContentUid => protected273289 (integer) title => protected'The Evolution of Nuclear Sub-Compartmentalization and its Impact on Genome F
            unction
' (83 chars) link => protected't3://page?uid=56937' (19 chars) imageReference => protectedTYPO3\CMS\Extbase\Domain\Model\FileReferenceprototypepersistent entity (uid=157084, pid=56624) uidLocal => protected345668 (integer) originalResource => protectedNULL uid => protected157084 (integer) _localizedUid => protected157084 (integer)modified _languageUid => protected0 (integer)modified _versionedUid => protected157084 (integer)modified pid => protected56624 (integer) image => protectedNULL textItems => protectedTYPO3\CMS\Extbase\Persistence\ObjectStorageprototypeobject (3 items) 0000000000000a1a0000000000000000 => FelixNagel\GenericGallery\Domain\Model\TextItemprototypepersistent entity (uid=24, pid=56624) bodytext => protected'<p>Main Supervisor:&nbsp;<a href="https://www.helmholtz-munich.de/en/ies/res
                  earch-groups/battich-lab" target="_blank">Dr. Nicolas Battich</a><br /> Grou
                  p:&nbsp;<a href="https://www.helmholtz-munich.de/en/ies/research-groups/batt
                  ich-lab" target="_blank">Battich Lab</a><br /> Institute:&nbsp;<a href="http
                  s://www.helmholtz-munich.de/en/ies" target="_blank">Institute of Epigenetics
                   and Stem Cells</a>,&nbsp;<a href="https://www.helmholtz-munich.de/en/comput
                  ational-health-center" target="_blank">Institute of Computational Biology</a
                  >,&nbsp;<a href="https://www.pioneercampus.org/" target="_blank">Helmholtz P
                  ioneer Campus</a>, Helmholtz Center Munich</p> <p>Collaborating Supervisor:
                   Dr. Joseph Marsh<br /> Group:<a href="https://www.wcb.ed.ac.uk/research/all
                  shire" target="_blank">&nbsp;</a><a href="https://www.ed.ac.uk/mrc-human-gen
                  etics-unit/research/marsh-group" target="_blank">Marsh Lab</a><br /> Institu
                  te:&nbsp;<a href="https://www.ed.ac.uk/mrc-human-genetics-unit" target="_bla
                  nk">MRC Human Genetics Unit</a>, Institute of Genetics and Cancer, Universit
                  y of Edinburgh</p>
' (1082 chars) position => protected'0,0' (3 chars) width => protected'0' (1 chars) uid => protected24 (integer) _localizedUid => protected24 (integer)modified _languageUid => protectedNULL _versionedUid => protected24 (integer)modified pid => protected56624 (integer)
00000000000009ee0000000000000000 => FelixNagel\GenericGallery\Domain\Model\TextItemprototypepersistent entity (uid=25, pid=56624) bodytext => protected'<p>Project Description:</p> <p>The project aims to address the evolutionary
                   dynamics of the different sub-compartments of the nucleus of eukaryotic cel
                  ls and reveal how they relate to genome function. The compartmentalization o
                  f the nucleus into functional condensates, so-called membraneless organelles
                   (MLOs), contributes to transcriptional regulation. Some MLOs form by liquid
                  -liquid phase separation in the cytoplasm and nucleoplasm of eukaryotic cell
                  s and have been tightly linked to different aspects of RNA biogenesis and me
                  tabolism. Homeostatic changes in MLOs occur during differentiation, and are
                  also associated with diseases, including cancers and viral infections. In th
                  e nucleus, the most prominent MLOs are nucleoli, which are sites dedicated t
                  o the transcription of ribosomal RNA. Other nuclear MLOs include: 1) Cajal b
                  odies (CBs) that are small compartments forming on active loci of small nucl
                  ear (sn)RNA transcription, typically observed in cells with high transcripti
                  onal and splicing demands, 2) nuclear speckles (NSs), which interact with ac
                  tive genes and represent hubs for pre-mRNA synthesis and metabolism, 3) para
                  speckles, compartments involved in the regulation of gene expression, and 4)
                   PML (promyelocytic leukemia) nuclear bodies (PML-NBs), which play a role in
                   SUMOylation and interact with chromatin, transcriptional regulators, and pr
                  oteins involved in DNA damage response and apoptosis. PML-NBs are also thoug
                  ht to function as hubs for protein modification in the nucleus, and to contr
                  ol the rate of cell cycle progression. Recent evidence suggests that differe
                  nt MLOs share homeostatic regulators, however their functional and evolution
                  ary links remain poorly understood. This project comprises of three parts: P
                  1) to reconstruct the shared evolutionary history of the core protein and no
                  n-coding RNA components of the different nuclear MLOs, using phylogenetic, s
                  tructural bioinformatics and molecular evolution tools (Marsh lab). P2) to r
                  eveal how MLO evolution ...
' (2812 chars) position => protected'0,0' (3 chars) width => protected'0' (1 chars) uid => protected25 (integer) _localizedUid => protected25 (integer)modified _languageUid => protectedNULL _versionedUid => protected25 (integer)modified pid => protected56624 (integer)
00000000000009e60000000000000000 => FelixNagel\GenericGallery\Domain\Model\TextItemprototypepersistent entity (uid=26, pid=56624) bodytext => protected'<p>Relevant Literature:</p> <ul> <li>Berchtold D, Battich N, Pelkmans L, 2
                  018, A systems-level study reveals regulators of membrane-less organelles in
                   human cells, Molecular Cell, 72, 6, 1035-1049.e5</li> <li>Battich N, Beume
                  r J, de Barbanson B, Krenning L, Chloé B, Tanenbaum M, Clevers H, van Ouden
                  aarden A, 2020, Sequencing metabolically labeled transcripts in single cells
                   reveals mRNA turnover strategies, Science, 367, 6482, 1151-1156</li> <li>I
                  lik İA, Malszycki M, Lübke AK, Schade C, Meierhofer D, Aktaş T, 2020, ON
                  and SRRM2 are essential for nuclear speckle formation, eLife, 9, e60579</li>
                   <li>Hirose T, Ninomiya K, Nakagawa S, Yamazaki T, 2022, A guide to membran
                  eless organelles and their various roles in gene regulation, Nat Rev Mol Cel
                  l Biol, online ahead of print.</li> <li>Badonyi M, Marsh JA, 2022, Large pr
                  otein complex interfaces have evolved to promote cotranslational assembly, e
                  Life, 10, e79602</li> </ul>
' (939 chars) position => protected'0,0' (3 chars) width => protected'0' (1 chars) uid => protected26 (integer) _localizedUid => protected26 (integer)modified _languageUid => protectedNULL _versionedUid => protected26 (integer)modified pid => protected56624 (integer)
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0000000000000a150000000000000000 => FelixNagel\GenericGallery\Domain\Model\GalleryItemprototypepersistent entity (uid=31, pid=56624) ttContentUid => protected273289 (integer) title => protected'Incorporating DNA methylation of the sex chromosomes in population research' (75 chars) link => protected't3://page?uid=56938' (19 chars) imageReference => protectedTYPO3\CMS\Extbase\Domain\Model\FileReferenceprototypepersistent entity (uid=157085, pid=56624) uidLocal => protected345669 (integer) originalResource => protectedNULL uid => protected157085 (integer) _localizedUid => protected157085 (integer)modified _languageUid => protected0 (integer)modified _versionedUid => protected157085 (integer)modified pid => protected56624 (integer) image => protectedNULL textItems => protectedTYPO3\CMS\Extbase\Persistence\ObjectStorageprototypeobject (3 items) 0000000000001e3c0000000000000000 => FelixNagel\GenericGallery\Domain\Model\TextItemprototypepersistent entity (uid=27, pid=56624) bodytext => protected'<p>Supervisor:&nbsp;<a href="http://www.helmholtz-munich.de/en/ame/pi/melani
                  e-waldenberger" target="_blank">Dr. Melanie Waldenberger</a><br /> Group:&nb
                  sp;<a href="http://www.helmholtz-munich.de/en/ame/research-groups/complex-di
                  seases" target="_blank">Research Unit Molecular Epidemiology</a><br /> Insti
                  tute:&nbsp;<a href="http://www.helmholtz-munich.de/en/epi" target="_blank">I
                  nstitute of Epidemiology</a>, Helmholtz Center Munich</p> <p>Collaborating
                  Supervisor: Dr. Kathryn Evans<br /> Group:&nbsp;<a href="https://www.ed.ac.u
                  k/centre-genomic-medicine/research-groups/evans-group" target="_blank">Centr
                  e for Genomic and Experimental Medicine</a>, Institute for Genetics and Canc
                  er, the University of Edinburgh<br /> Institute:&nbsp;<a href="https://www.e
                  d.ac.uk/centre-genomic-medicine" target="_blank">Centre for Genomic and Expe
                  rimental Medicine</a>,&nbsp;<a href="https://www.ed.ac.uk/institute-genetics
                  -cancer" target="_blank">Institute for Genetics and Cancer</a>, the Universi
                  ty of Edinburgh</p>
' (1007 chars) position => protected'0,0' (3 chars) width => protected'0' (1 chars) uid => protected27 (integer) _localizedUid => protected27 (integer)modified _languageUid => protectedNULL _versionedUid => protected27 (integer)modified pid => protected56624 (integer)
00000000000009e30000000000000000 => FelixNagel\GenericGallery\Domain\Model\TextItemprototypepersistent entity (uid=28, pid=56624) bodytext => protected'<p>Human disease phenotypes often manifest differently by sex, including age
                   of onset, disease incidence, symptoms and response to therapy. DNA methylat
                  ion is an epigenetic modification involving the covalent transfer of a methy
                  l group to the 5’ carbon of cytosine residues.&nbsp; Methylation of DNA pl
                  ays a key role in determining genomic structure and function, including regu
                  lation of cellular differentiation and gene expression. Population-based stu
                  dies often use the Illumina Infinium HumanMethylation450 and MethylationEPIC
                   BeadChip arrays which offer costeffective measurement of DNA methylation at
                   &gt; 450,000 and &gt; 850,000 loci across all chromosomes and allow profili
                  ng at a large scale. Such research over the last decade has showed that diff
                  erential DNA methylation of the autosomes is implicated in a variety of comp
                  lex multifactorial diseases. However, X and Y chromosome data have mostly be
                  en excluded due to the analytical complexity associated with sex chromosome
                  dosage differences and the impact of X-chromosome inactivation. On the autos
                  omes, DNA methylation is quantified as an average of both alleles, as they t
                  ypically have similar DNA methylation levels (with the exception of imprinte
                  d loci). However, the inactivation of one X chromosome in females to ensure
                  dosage compensation leads to the active and inactive X chromosomes having di
                  stinct DNA methylation profiles. In this project, we will develop an analyti
                  cal pipeline for X and Y chromosome data preprocessing, including quality co
                  ntrol, normalization, and batch correction steps. We aim to explore (1) the
                  impact of DNA methylation at the X and Y chromosomes on human disease phenot
                  ypes e.g. on sex hormone levels, (2) their interaction with related molecula
                  r layers like gene expression, histone marks or plasma proteins and (3) the
                  impact of environmental factors like tobacco smoking. To do this, we build o
                  n existing DNA methylation data of two large and wellcharacterized cohort st
                  udies (see below) with t...
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00000000000009df0000000000000000 => FelixNagel\GenericGallery\Domain\Model\TextItemprototypepersistent entity (uid=29, pid=56624) bodytext => protected'<p>Relevant Literature:</p> <ul> <li>Hawe JS, Wilson R, Schmid KT, Zhou L,
                   Lakshmanan LN, Lehne BC, Kühnel B, Scott WR, Wielscher M, Yew YW, Baumbach
                   C, Lee DP, Marouli E, Bernard M, Pfeiffer L, Matías-García PR, Autio MI,
                  Bourgeois S, Herder C, Karhunen V, Meitinger T, Prokisch H, Rathmann W, Rode
                  n M, Sebert S, Shin J, Strauch K, Zhang W, Tan WLW, Hauck SM, Merl-Pham J, G
                  rallert H, Barbosa EGV; MuTHER Consortium; Illig T, Peters A, Paus T, Pausov
                  a Z, Deloukas P, Foo RSY, Jarvelin MR, Kooner JS, Loh M, Heinig M, Gieger C,
                   Waldenberger M, Chambers JC. 2022. Genetic variation influencing DNA methyl
                  ation provides insights into molecular mechanisms regulating genomic functio
                  n. Nat Genet: 54(1):18-29</li> <li>Lohoff FW, Clarke TK, Kaminsky ZA, Walke
                  r RM, Bermingham ML, Jung J, Morris SW, Rosoff D, Campbell A, Barbu M, Charl
                  et K, Adams M, Lee J, Howard DM, O'Connell EM, Whalley H, Porteous DJ, McInt
                  osh AM, Evans KL. 2022. Epigenome-wide association study of alcohol consumpt
                  ion in N = 8161 individuals and relevance to alcohol use disorder pathophysi
                  ology: identification of the cystine/glutamate transporter SLC7A11 as a top
                  target. Mol Psychiatry Mar;27(3):1754-1764</li> <li>Walker RM, Bermingham M
                  L, Vaher K, Morris SW, Clarke TK, Bretherick AD, Zeng Y, Amador C, Rawlik K,
                   Pandya K, Hayward C, Campbell A, Porteous DJ, McIntosh AM, Marioni RE, Evan
                  s KL. 2020. Epigenome-wide analyses identify DNA methylation signatures of d
                  ementia risk. Alzheimers Dement (Amst). Aug 10;12(1):e12078</li> <li>Gadd D
                  A, Hillary RF, McCartney DL, Zaghlool SB, Stevenson AJ, Cheng Y, Fawns-Ritch
                  ie C, Nangle C, Campbell A, Flaig R, Harris SE, Walker RM, Shi L, Tucker-Dro
                  b EM, Gieger C, Peters A, Waldenberger M, Graumann J, McRae AF, Deary IJ, Po
                  rteous DJ, Hayward C, Visscher PM, Cox SR, Evans KL, McIntosh AM, Suhre K, M
                  arioni RE. 2022. Epigenetic scores for the circulating proteome as tools for
                   disease prediction. Elife: 11:e71802</li> <li>Singmann P, Shem-Tov D, Wahl
                   S, Grallert H, Fiorito ...
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galleryType => 'single' (6 chars) gallerySettings => array(5 items) name => 'Gallery' (7 chars) icon => 'extensions-generic-gallery' (26 chars) template => 'fileadmin/0-templates/Portalseiten_NEU/ext/tx_genericgallery/Private/Templat
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            rying growth conditions
' (99 chars) link => protected't3://page?uid=56630' (19 chars) imageReference => protectedTYPO3\CMS\Extbase\Domain\Model\FileReferenceprototypepersistent entity (uid=157129, pid=56624) uidLocal => protected345694 (integer) originalResource => protectedNULL uid => protected157129 (integer) _localizedUid => protected157129 (integer)modified _languageUid => protected0 (integer)modified _versionedUid => protected157129 (integer)modified pid => protected56624 (integer) image => protectedNULL textItems => protectedTYPO3\CMS\Extbase\Persistence\ObjectStorageprototypeobject (3 items) 00000000000010090000000000000000 => FelixNagel\GenericGallery\Domain\Model\TextItemprototypepersistent entity (uid=30, pid=56624) bodytext => protected'<p>Direct Supervisor: Dr. Kurt Schmoller<br /> Group:&nbsp;<a href="https://
                  www.helmholtz-munich.de/en/ife/research-groups/schmoller-lab" target="_blank
                  ">Cell and Organelle Size Control</a><br /> Institute:&nbsp;<a href="https:/
                  /www.helmholtz-munich.de/en/ife" target="_blank">Functional Epigenetics</a>,
                   Helmholtz Center Munich</p> <p>Collaborating Supervisor: Dr. Matthew Swaff
                  er<br /> Group:&nbsp;<a href="https://www.wcb.ed.ac.uk/" target="_blank">Wel
                  lcome Trust Centre for Cell Biology, Swaffer Group</a><br /> Institute:&nbsp
                  ;<a href="https://www.wcb.ed.ac.uk/" target="_blank">Wellcome Trust Centre f
                  or Cell Biology</a>, University of Edinburgh</p>
' (656 chars) position => protected'0,0' (3 chars) width => protected'0' (1 chars) uid => protected30 (integer) _localizedUid => protected30 (integer)modified _languageUid => protectedNULL _versionedUid => protected30 (integer)modified pid => protected56624 (integer)
000000000000100c0000000000000000 => FelixNagel\GenericGallery\Domain\Model\TextItemprototypepersistent entity (uid=31, pid=56624) bodytext => protected'<p>Project Description:</p> <p>Cells must constantly balance and adjust the
                   precise composition of their proteome in response to external and internal
                  cues. For many proteins, this requires matching their synthesis rates with t
                  he size and growth rate of the cell. For example, ribosomes and other biosyn
                  thetic machinery are tightly correlated with growth across a range of condit
                  ions. However, specific subsets of proteins need to be regulated differently
                   – one of the best examples of this is chromatin. Chromatinassociated prot
                  eins, including core histone proteins, are directly coupled to DNA amount, a
                  nd therefore cell cycle, but are independent of cell size or growth rate. Th
                  is ensures that histones are kept at a 1-to-1 ratio with the genome, such th
                  at the structure, composition, and function of chromatin can always be maint
                  ained.</p> <p><br /> Due to this variable requirement for different protein
                   sectors, the proteome is constantly remodelled whenever cell size, cellular
                   growth rate or cell cycle change. Ensuring correct proteome composition is
                  therefore particularly challenging when moving between different environment
                  al conditions, because, depending on the nutrients, all three of these param
                  eters will change.</p> <p><br /> Our preliminary results show that in buddi
                  ng yeast, maintaining constant amounts of histones across different environm
                  ental conditions requires both transcriptional and post-transcriptional regu
                  latory controls. In this project, we will use a combination of single-cell i
                  maging, quantitative functional genomics and high-throughput proteomics to d
                  etermine how the production of other key chromatin components is regulated a
                  s cells move between different nutritional states. In addition, we will also
                   examine more generally how other proteome sectors are regulated in response
                   to altered environmental conditions. After characterizing the proteome comp
                  osition and revealing whether the responsible regulation is transcriptional
                  or post-transcriptional ...
' (2458 chars) position => protected'0,0' (3 chars) width => protected'0' (1 chars) uid => protected31 (integer) _localizedUid => protected31 (integer)modified _languageUid => protectedNULL _versionedUid => protected31 (integer)modified pid => protected56624 (integer)
0000000000001def0000000000000000 => FelixNagel\GenericGallery\Domain\Model\TextItemprototypepersistent entity (uid=32, pid=56624) bodytext => protected'<p>Relevant Literature:</p> <ul> <li>Swaffer MP, Marinov GK, Zheng H, Jone
                  s AW, Greenwood J, Kundaje A, Snijders AP, Greenleaf WJ, Reyes-Lamothe R, Sk
                  otheim JM, 2022, RNA polymerase II dynamics and mRNA stability feedback dete
                  rmine mRNA scaling with cell size, bioRxiv,&nbsp;<a href="https://doi.org/10
                  .1101/2021.09.20.461005" target="_blank">https://doi.org/10.1101/2021.09.20.
                  461005</a></li> <li>Seel A, Padovani F, Finster A, Mayer M, Bureik D, Osman
                   C, Klecker T, Schmoller KM, 2021, Regulation with cell size ensures mitocho
                  ndrial DNA homeostasis during cell growth, bioRxiv,&nbsp;<a href="http://doi
                  .org/10.1101/2021.12.03.471050" target="_blank">doi.org/10.1101/2021.12.03.4
                  71050</a></li> <li>Swaffer MP, Kim J, Chandler-Brown D, Langhinrichs M, Mar
                  inov GK, Greenleaf WJ, Kundaje A, Schmoller KM, Skotheim JM, 2021, Transcrip
                  tional chromatin-based partitioning mechanisms uncouple protein scaling from
                   cell cell size, Molecular Cell, 81, 1-15</li> <li>Claude K-L, Bureik D, Ch
                  atzitheodoridou D, Adarska P, Singh A, Schmoller KM, 2020, Transcription coo
                  rdinates histone amounts and genome content, Nature Communications, 12, 4202
                  </li> <li>Kukhtevich IV, Lohrberg N, Padovani F, Schneider R, Schmoller KM,
                   2020, Cell size sets the diameter of the budding yeast contractile ring, Na
                  ture Communications, 22, 2952</li> </ul>
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imageProperties => protectedNULL uid => protected32 (integer) _localizedUid => protected32 (integer)modified _languageUid => protectedNULL _versionedUid => protected32 (integer)modified pid => protected56624 (integer)
0000000000000feb0000000000000000 => FelixNagel\GenericGallery\Domain\Model\GalleryItemprototypepersistent entity (uid=33, pid=56624) ttContentUid => protected273331 (integer) title => protected'Single cell to lineage analysis of epimutation establishment and heritabilit
            y in response to external insults such as antifungal agents
' (135 chars) link => protected't3://page?uid=56626' (19 chars) imageReference => protectedTYPO3\CMS\Extbase\Domain\Model\FileReferenceprototypepersistent entity (uid=157130, pid=56624) uidLocal => protected345693 (integer) originalResource => protectedNULL uid => protected157130 (integer) _localizedUid => protected157130 (integer)modified _languageUid => protected0 (integer)modified _versionedUid => protected157130 (integer)modified pid => protected56624 (integer) image => protectedNULL textItems => protectedTYPO3\CMS\Extbase\Persistence\ObjectStorageprototypeobject (3 items) 000000000000104d0000000000000000 => FelixNagel\GenericGallery\Domain\Model\TextItemprototypepersistent entity (uid=33, pid=56624) bodytext => protected'<p>Direct Supervisor: Dr. Maria Colomé Tatché<br /> Group:&nbsp;<a href="h
                  ttps://backup.helmholtz-munich.de/icb/research/groups/computational-epigenom
                  ics/overview/index.html" target="_blank">Computational Epigenomics</a><br />
                   Institute:&nbsp;<a href="https://www.helmholtz-muenchen.de/icb/index.html"
                  target="_blank">Institute for Computational Biology&nbsp;</a>, Helmholtz Cen
                  ter Munich</p> <p>Collaborating Supervisor: Dr. Robin Allshire<br /> Group:
                  <a href="https://www.wcb.ed.ac.uk/research/allshire" target="_blank">&nbsp;A
                  llshire Lab</a><br /> Institute:&nbsp;<a href="https://www.wcb.ed.ac.uk/" ta
                  rget="_blank">Wellcome Centre for Cell Biology</a>, Institute of Cell Biolog
                  y, School of Biological Sciences, University of Edinburgh</p>
' (745 chars) position => protected'0,0' (3 chars) width => protected'0' (1 chars) uid => protected33 (integer) _localizedUid => protected33 (integer)modified _languageUid => protectedNULL _versionedUid => protected33 (integer)modified pid => protected56624 (integer)
0000000000001de90000000000000000 => FelixNagel\GenericGallery\Domain\Model\TextItemprototypepersistent entity (uid=34, pid=56624) bodytext => protected'<p>Project Description:</p> <p>Fungal survival in harsh environments involv
                  es stress-sensing pathways that reprogram their proteomes. New conditions, i
                  ncluding climate change, can push opportunistic fungi to colonise novel nich
                  es, potentially becoming harmful pathogens. Effective antifungal/fungicide t
                  reatment&nbsp; are limited in number precisely because fungi are adept at re
                  sisting challenges. Antifungal resistance is increasingly prevalent, raising
                   fungal borne disease frequencies in humans and crops1. Conventional wisdom
                  that resistance results solely from genetic mutations was overturned by our
                  discovery that external insults selects for cells with a distinct epigenetic
                   landscape - repressive heterochromatin over various genes whose reduced exp
                  ression confers resistance (e.g. mitochondrial proteins)2,3. Such heterochro
                  matin-dependent ‘epimutations’ are unstable, slowly losing resistance up
                  on external insult removal. We hypothesize that extracellular stresses, incl
                  uding fungicides widely used in agriculture, reprogramme fungal epigenomes s
                  o that they transiently acquire heterochromatin at locations which confer he
                  ritable, but unstable, resistance. By employing single cell analysis of line
                  ages seeded by just one cell we aim to provide insight into the mechanisms u
                  tilized by cells to mediate epimutant-mediated resistance. This project will
                   combine the power of classic Luria-Delbruck fluctuation tests with low cell
                   number/single cell (ATAC-seq, Cut&amp;Tag and RNA-seq) sequencing workflows
                   to dissect the events that result in the emergence of transiently antifunga
                  l/fungicide resistant lineages due to epimutation formation.</p>
' (1660 chars) position => protected'0,0' (3 chars) width => protected'0' (1 chars) uid => protected34 (integer) _localizedUid => protected34 (integer)modified _languageUid => protectedNULL _versionedUid => protected34 (integer)modified pid => protected56624 (integer)
000000000000102a0000000000000000 => FelixNagel\GenericGallery\Domain\Model\TextItemprototypepersistent entity (uid=35, pid=56624) bodytext => protected'<p>Relevant Literature:</p> <ul> <li>Fisher MC, Hawkins NJ, Sanglard D.
                  &amp; Gurr SJ. (2018) Worldwide emergence of resistance to antifungal drugs
                  challenges human health and food security. Science 360, 739–742</li> <li>
                  Torres-Garcia S, Yaseen I, Shukla M, Audergon PNCB, White SA, Pidoux AL, All
                  shire RC. (2020). Epigenetic gene silencing by heterochromatin primes fungal
                   resistance. Nature 585, 453–458</li> <li>Yaseen I, White SA, Torres-Garc
                  ia S, Spanos C, Lafos M, Gaberdiel E, Yeboah R, El Karoui M, Rappsilber J, P
                  idoux AL, Allshire RC. (2022) Proteasome-dependent truncation of the negativ
                  e heterochromatin regulator Epe1 mediates antifungal resistance. Nature Stru
                  cture &amp; Molecular Biology (in press); BioRXiv:&nbsp;<a href="https://doi
                  .org/10.1101/2021.12.20.473483" target="_blank">https://doi.org/10.1101/2021
                  .12.20.473483</a></li> <li>A. Danese, M.L. Richter, D.S. Fischer, F.J. Thei
                  s and M. Colomé-Tatché. EpiScanpy: integrated single-cell epigenomic analy
                  sis. Nat. Commun. 12, 5228 (2021).</li> <li>A. vd Graaf, R. Wardenaar, D.A.
                  
                  
                  imutations. Proc. Natl. Acad. Sci. USA 112:6676-81 (2015). (* cocorrespondin
                  g authors)</li> </ul>
' (1313 chars) position => protected'0,0' (3 chars) width => protected'0' (1 chars) uid => protected35 (integer) _localizedUid => protected35 (integer)modified _languageUid => protectedNULL _versionedUid => protected35 (integer)modified pid => protected56624 (integer)
imageProperties => protectedNULL uid => protected33 (integer) _localizedUid => protected33 (integer)modified _languageUid => protectedNULL _versionedUid => protected33 (integer)modified pid => protected56624 (integer)
0000000000001df10000000000000000 => FelixNagel\GenericGallery\Domain\Model\GalleryItemprototypepersistent entity (uid=34, pid=56624) ttContentUid => protected273331 (integer) title => protected'Targeting translocation-specific downstream signaling to treat MLL-AF4 rearr
            anged leukaemia
' (91 chars) link => protected't3://page?uid=56627' (19 chars) imageReference => protectedTYPO3\CMS\Extbase\Domain\Model\FileReferenceprototypepersistent entity (uid=157131, pid=56624) uidLocal => protected345692 (integer) originalResource => protectedNULL uid => protected157131 (integer) _localizedUid => protected157131 (integer)modified _languageUid => protected0 (integer)modified _versionedUid => protected157131 (integer)modified pid => protected56624 (integer) image => protectedNULL textItems => protectedTYPO3\CMS\Extbase\Persistence\ObjectStorageprototypeobject (3 items) 00000000000010260000000000000000 => FelixNagel\GenericGallery\Domain\Model\TextItemprototypepersistent entity (uid=36, pid=56624) bodytext => protected'<p>Direct Supervisor: Prof. Dr. Irmela Jeremias<br /> Group:&nbsp;<a href="h
                  ttps://backup.helmholtz-munich.de/en/ahs/index.html" target="_blank">Researc
                  h Unit Apoptosis in Hematopoietic Stem Cells</a><br /> institute:<a href="ht
                  tps://www.helmholtz-munich.de/en/stem-cells" target="_blank">&nbsp;Institute
                   of Stem Cell Research</a>, Helmholtz Center Munich</p> <p>Collaborating Su
                  pervisor: Dr. Katrin Ottersbach<br /> Group:&nbsp;<a href="https://www.ed.ac
                  .uk/regenerative-medicine/research/katrin-ottersbach" target="_blank">Otters
                  bach Group</a><br /> Institute:&nbsp;<a href="https://www.ed.ac.uk/regenerat
                  ive-medicine" target="_blank">Centre for Regenerative Medicine</a>, Universi
                  ty of Edinburgh</p>
' (703 chars) position => protected'0,0' (3 chars) width => protected'0' (1 chars) uid => protected36 (integer) _localizedUid => protected36 (integer)modified _languageUid => protectedNULL _versionedUid => protected36 (integer)modified pid => protected56624 (integer)
00000000000010320000000000000000 => FelixNagel\GenericGallery\Domain\Model\TextItemprototypepersistent entity (uid=37, pid=56624) bodytext => protected'<p>Project Description:</p> <p>Translocation t(4;11) drives highly aggressi
                  ve MLL-AF4 (KMT2A-AFF1) positive acute leukemias, associated with poor progn
                  osis. Due to the aberrant fusion of the two epigenetic regulators, MLL and A
                  F4, and recruitment of their associated complexes, MLL-AF4 positive leukaemi
                  a is characterized by multiple epigenetic changes which drive the malignant
                  disease. MLL is a positive regulator of gene expression by mediating e.g. H3
                  K4 methylation. AF4 is the central scaffold protein of the super elongation
                  complex (SEC), which increases the catalytic rate of RNA polymerase II trans
                  cription. The transcriptional changes caused by the MLL-AF4 driver mutation
                  that result in various leukemic outcomes are largely unknown. A better under
                  standing of the mechanisms responsible for disease progression is a prerequi
                  site to developing innovative, targeted and efficient treatment to improve t
                  he prognosis of patients.</p> <p><br /> Previously, the two PIs in Edinburg
                  h and Munich have studied MLL-AF4 positive leukaemia using complementary in
                  vivo models. In syngeneic mice, we recently showed that distinct microRNAs a
                  nd their dysregulated targets are important downstream mediators of MLL-AF4-
                  driven leukemic growth and lineage choice (Malouf et al, Blood 2021). Using
                  patient-derived xenograft models, we recently demonstrated that MLL-AF4 posi
                  tive leukaemia remains dependent on the MLL-AF4 translocation, also when est
                  ablished patient-derived xenograft (PDX) leukaemia grows in mice (Carlet et
                  al., Nature Comm. 2021).</p> <p><br /> We now plan to join forces in a sear
                  ch for downstream signaling molecules which are upregulated by MLL-AF4 and r
                  elevant for leukaemia survival and growth. To study the functional relevance
                   of published and own candidate genes, we will use CRISPR/Cas9 knockout scre
                  ens in existing MLL-AF4 positive PDX leukaemia models in vivo, followed by s
                  ingle gene validation. Epigenetic changes induced by the genetic interventio
                  n will be monitored usin...
' (2588 chars) position => protected'0,0' (3 chars) width => protected'0' (1 chars) uid => protected37 (integer) _localizedUid => protected37 (integer)modified _languageUid => protectedNULL _versionedUid => protected37 (integer)modified pid => protected56624 (integer)
000000000000103e0000000000000000 => FelixNagel\GenericGallery\Domain\Model\TextItemprototypepersistent entity (uid=38, pid=56624) bodytext => protected'<p>Relevant Literature:</p> <ul> <li>Malouf C, Antunes ETB, O'Dwyer M, Jak
                  obczyk H, Sahm F, Landua SL, Anderson RA, Soufi A, Halsey C and K. Ottersbac
                  h (2021) “miR-130b and miR-128a are essential lineage-specific codrivers o
                  f t(4;11) MLL-AF4 acute leukemia.” Blood. 2021 Nov 25;138(21):2066-2092</l
                  i> <li>Symeonidou V, Jakobczyk H, Bashanfer S, Malouf C, Fotopoulou F, Kote
                  cha RS, Anderson RA, Finch AJ and K. Ottersbach (2021) “Defining the fetal
                   origin of MLL-AF4 infant leukemia highlights specific fatty acid requiremen
                  ts.” Cell Rep. 37(4):109900</li> <li>Carlet M, Völse K, Vergalli J, Beck
                  er M, Herold T, Arner A, Senft D, Jurinovic V, Liu WH, Gao Y, Dill V, Fehse
                  B, Baldus CD, Bastian L, Lenk L, Schewe DM, Bagnoli JW, Vick B, Schmid JP, W
                  ilhelm A, Marschalek R, Jost PJ, Miething C, Riecken K, Schmidt-Supprian M,
                  Binder V and Jeremias I. (2021) „In vivo inducible reverse genetics in pat
                  ients' tumors to identify individual therapeutic targets.” Nat Commun. 202
                  1 Sep 27;12(1):5655</li> <li>Ebinger, S., E. Z. Ozdemir, C. Ziegenhain, S.
                  Tiedt, C. Castro Alves, M. Grunert, M. Dworzak, C. Lutz, V. A. Turati, T. En
                  ver, H. P. Horny, K. Sotlar, S. Parekh, K. Spiekermann, W. Hiddemann, A. Sch
                  epers, B. Polzer, S. Kirsch, M. Hoffmann, B. Knapp, J. Hasenauer, H. Pfeifer
                  , R. Panzer-Grumayer, W. Enard, O. Gires and I. Jeremias (2016). "Characteri
                  zation of Rare, Dormant, and Therapy-Resistant Cells in Acute Lymphoblastic
                  Leukemia." Cancer Cell 30(6): 849-862</li> </ul>
' (1492 chars) position => protected'0,0' (3 chars) width => protected'0' (1 chars) uid => protected38 (integer) _localizedUid => protected38 (integer)modified _languageUid => protectedNULL _versionedUid => protected38 (integer)modified pid => protected56624 (integer)
imageProperties => protectedNULL uid => protected34 (integer) _localizedUid => protected34 (integer)modified _languageUid => protectedNULL _versionedUid => protected34 (integer)modified pid => protected56624 (integer)
0000000000001df50000000000000000 => FelixNagel\GenericGallery\Domain\Model\GalleryItemprototypepersistent entity (uid=35, pid=56624) ttContentUid => protected273331 (integer) title => protected'RNA modification in development and disease' (43 chars) link => protected't3://page?uid=56628' (19 chars) imageReference => protectedTYPO3\CMS\Extbase\Domain\Model\FileReferenceprototypepersistent entity (uid=157132, pid=56624) uidLocal => protected345691 (integer) originalResource => protectedNULL uid => protected157132 (integer) _localizedUid => protected157132 (integer)modified _languageUid => protected0 (integer)modified _versionedUid => protected157132 (integer)modified pid => protected56624 (integer) image => protectedNULL textItems => protectedTYPO3\CMS\Extbase\Persistence\ObjectStorageprototypeobject (3 items) 00000000000010060000000000000000 => FelixNagel\GenericGallery\Domain\Model\TextItemprototypepersistent entity (uid=39, pid=56624) bodytext => protected'<p>Direct Supervisor: Prof. Dr. Robert Schneider<br /> Group:&nbsp;<a href="
                  https://www.helmholtz-munich.de/en/ife/research-groups/schneider-lab" target
                  ="_blank">Chromatin Dynamics and Epigenetics</a><br /> Institute:&nbsp;<a hr
                  ef="https://www.helmholtz-munich.de/en/ife" target="_blank">Institute of Fun
                  ctional Epigenetics</a>, Helmholtz Center Munich</p> <p>Collaborating Super
                  visor: Prof. Dónal O’Carroll&nbsp;<br /> Group:&nbsp;<a href="https://www
                  .ed.ac.uk/regenerative-medicine/research/donal-o-carroll" target="_blank">RN
                  A Function in Germ and Stem Cell Biology</a><br /> Institute:&nbsp;<a href="
                  https://www.ed.ac.uk/regenerative-medicine" target="_blank"><strong>Center f
                  or Regeneration and Repair&nbsp;</strong>Centre for Regenerative Medicine</a
                  >, University of Edinburgh</p>
' (790 chars) position => protected'0,0' (3 chars) width => protected'0' (1 chars) uid => protected39 (integer) _localizedUid => protected39 (integer)modified _languageUid => protectedNULL _versionedUid => protected39 (integer)modified pid => protected56624 (integer)
00000000000010480000000000000000 => FelixNagel\GenericGallery\Domain\Model\TextItemprototypepersistent entity (uid=40, pid=56624) bodytext => protected'<p>The emerging research field of ‘Epitranscriptomics’ tackles one of th
                  e next challenges for molecular biology: the understanding of how modificati
                  ons of RNAs affect the function of RNAs and of their vital role in cellular
                  homeostasis. Such modifications of RNAs occur on all types of cellular RNAs
                  and are involved in the regulation of diverse biological processes. Misregul
                  ated RNA methyltransferases have been found in multiple cancer types and are
                   promising targets for a new generation of anti-cancer drugs.</p> <p><br />
                   Recent breakthroughs have transformed our understanding of the epitranscrip
                  tome and allow us now to interrogate RNA modifications at an unprecedented s
                  cale. The epitranscriptome constitutes a new layer of (epi)genetic informati
                  on and will thus change the way how we look at RNA and also open new avenues
                   to identify novel druggable pathways. We recently identified two novel RNA
                  methyltransferases and revealed their function in vitro and in animals creat
                  ing new models for human diseases (Ignatova et al., 2020a; Ignatova et al.,
                  2020b).</p> <p><br /> The aim of the project, joint with the O’Carroll la
                  b will be i) to identify potential methyltransferases, and their targets and
                   to (ii) unravel the role of the respective modification(s) by applying a co
                  mbination of in vitro and in vivo assays. We will build on the expertise in
                  our laboratory in the identification of novel modifying enzymes and in genom
                  e-wide mapping of modifications as well as on the expertise of the O’Carro
                  ll lab in cellular manipulations and mouse and cancer models.</p> <p><br />
                   This project includes the possibility to be part of a dynamic and internati
                  onal team and to learn state of the art technologies both in Munich and Edin
                  burgh (such as novel NGS based approaches to map RNA modifications and their
                   bioinformatic analysis in low to single cells, as wells as ES cell and mous
                  e models, Crispr/Cas9/Cas13 mediated manipulations, advanced imaging techniq
                  ues, biochemical approac...
' (2629 chars) position => protected'0,0' (3 chars) width => protected'0' (1 chars) uid => protected40 (integer) _localizedUid => protected40 (integer)modified _languageUid => protectedNULL _versionedUid => protected40 (integer)modified pid => protected56624 (integer)
000000000000108d0000000000000000 => FelixNagel\GenericGallery\Domain\Model\TextItemprototypepersistent entity (uid=41, pid=56624) bodytext => protected'<p>Relevant Literature:</p> <ul> <li>Ignatova, V.V., Kaiser, S., Sook Yuin
                  , S., Bing, X., Stolz, P., Tan, Y.X., Xim Tan, Y., Leng Lee, C., Hoon Gay, F
                  .P., Rico Lastres, P.,Gerlini, R., Rathkolb, B., Aguilar-Pimentel., A. Sanz-
                   Moreno, A., Klein-Rodewald, T., Calzada-Wack, J., Ibragimov, E., Valenta, M
                  ., Lukauskas, S., Marscha, S., Leuchtenberger, S., Fuchs, H., Gaius-Durner,
                  V., Hrabe de Angelis, M., Bultmann, S., Rando, O.J., Guccione, E., Kellner,
                  S.M. and Schneider, R. (2020) METTL6 is a tRNA m3C methyltransferase that re
                  gulates pluripotency and tumor cell growth. Science Advances, 6, eaaz4551</l
                  i> <li>Zoch, A., Auchynnikava, T., Berrens, R. V., Kabayama, Y., Schöpp, T
                  ., Heep, M., Vasiliauskaitė, L., Pérez-Rico, Y. A., Cook, A. G., Shkumatav
                  a, A., Rappsilber, J., Allshire, R. C. and O'Carroll, D. (2020) SPOCD1 is an
                   essential executor of piRNA-directed 1 de novo DNA methylation. Nature 584,
                   635-639</li> <li>Ignatova, V.V., Stolz, P., Kaiser, S., Gustafsson, T.H.,
                  Rico Lastres, P., Sanz-Moreno, A., Cho, Y.L., Amarie, O.V., Aguilar-Pimentel
                  , A., Klein-Rodewald, T., Calzada-Wack, J., Becker, L., Marschall, S., Kraig
                  er, M., Garrett, L., Seisenberger, C., Hölter, S.M., Borland, K., Van De Lo
                  gt, E., Jansen, P., Baltissen, M.P., Vermeulen, M., Wurst, W., Gailus-Durner
                  , V., Fuchs, H., Hrabe de Angelis, M., Rando, O.J., Kellner, S.M., Bultmann,
                   S. and Schneider. R. (2020) The rRNA m6A methyltransferase METTL5 regulates
                   pluripotency and developmental programmes. Genes and Development , 34, 715-
                  729</li> <li>Morgan, M., Much, C., DiGiacomo, M., Azzi, C., Ivanova, I., Vi
                  tsios, D. M., Pistolic, J., Collier, P., Ventura De Oliveira Moreira, P., Be
                  nes, V., Enright, A. J. and O'Carroll, D. (2017) mRNA 3ʹ uridylation and po
                  ly(A) tail length sculpt the mammalian maternal transcriptome Nature 548, 34
                  7-351</li> </ul>
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00000000000010410000000000000000 => FelixNagel\GenericGallery\Domain\Model\GalleryItemprototypepersistent entity (uid=36, pid=56624) ttContentUid => protected273331 (integer) title => protected'Mechanisms of context-specific glucocorticoid gene regulation inferred from
            transcriptional bursting kinetics
' (109 chars) link => protected't3://page?uid=56629' (19 chars) imageReference => protectedTYPO3\CMS\Extbase\Domain\Model\FileReferenceprototypepersistent entity (uid=157133, pid=56624) uidLocal => protected345690 (integer) originalResource => protectedNULL uid => protected157133 (integer) _localizedUid => protected157133 (integer)modified _languageUid => protected0 (integer)modified _versionedUid => protected157133 (integer)modified pid => protected56624 (integer) image => protectedNULL textItems => protectedTYPO3\CMS\Extbase\Persistence\ObjectStorageprototypeobject (3 items) 000000000000103d0000000000000000 => FelixNagel\GenericGallery\Domain\Model\TextItemprototypepersistent entity (uid=42, pid=56624) bodytext => protected'<p>Main Supervisor: Prof. Dr. Nina Henriette Uhlenhaut<br /> Group: Division
                   Molecular Endocrinology<br /> Institute:<a href="https://www.helmholtz-muni
                  ch.de/en/hdc" target="_blank">&nbsp;Institute for Diabetes and Endocrinology
                  </a></p> <p>Collaborating Supervisor: Prof. Dr. Ramon Grima<br /> Group:&nb
                  sp;<a href="https://grimagroup.bio.ed.ac.uk/" target="_blank">Grima Group</a
                  >, Institute of Quantitative Biology, Biochemistry and Biotechnology<br /> I
                  nstitute:<a href="https://www.ed.ac.uk/biology/quantitative-biology-biochemi
                  stry-biotechnology" target="_blank">&nbsp;Institute of Quantitative Biology,
                   Biochemistry and Biotechnology</a>, School of Biological Sciences, Universi
                  ty of Edinburgh</p>
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00000000000010650000000000000000 => FelixNagel\GenericGallery\Domain\Model\TextItemprototypepersistent entity (uid=43, pid=56624) bodytext => protected'<p>Project Description:</p> <p>Glucocorticoids are widely prescribed anti-i
                  nflammatory drugs in the treatment of COVID-19, asthma, sepsis and others. H
                  owever, chronic and systemic treatment comes with severe adverse effects lik
                  e diabetes type 2, obesity, osteoporosis, muscle atrophy etc. Molecularly, g
                  lucocorticoids diffuse across the cellular membrane and engage with the gluc
                  ocorticoid receptor (GR), which translocates into the nucleus. In the nucleu
                  s, the GR binds glucocorticoid response elements and represses as well as ac
                  tivates target gene expression. Interestingly, gene activation is a hallmark
                   of glucocorticoid-mediated side effects in metabolic tissues, whereas gene
                  repression is associated with its anti-inflammatory function. Therefore, the
                   Uhlenhaut Lab is exploring the molecular circuits employed by the GR to und
                  erstand gene repression versus activation; a biological conundrum not only r
                  estricted to nuclear hormone receptors. Our aim is to identify new therapeut
                  ically targets to improve glucocorticoid therapy and reduce adverse effects.
                  </p> <p><br /> In recent years, we have studied the molecular mechanisms of
                   gene activation versus repression in macrophages using next-generation sequ
                  encing technologies and were able to describe factors required for gene acti
                  vation in a gene-specific manner. We also discovered that the chromatin stat
                  es at glucocorticoid binding sites associated with gene repression are highl
                  y diverse, pointing towards gene-specific repression mechanisms employed by
                  the glucocorticoid receptor. Those observations are in line with the diverse
                   mechanisms described in the literature.</p> <p><br /> In this project, we
                  will explore the molecular mechanisms employed by GR in the regulation of in
                  flammatory gene expression. We will use the bacteriophage-derived RNA stem-l
                  oops as transcriptional reporters co-expressed with fluorescently labelled c
                  oat proteins (MS2/MCP and PP7/PCP) in combination with CRISPR/Cas9-mediated
                  gene targeting to monito...
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0000000000001de80000000000000000 => FelixNagel\GenericGallery\Domain\Model\TextItemprototypepersistent entity (uid=44, pid=56624) bodytext => protected'<p>Relevant Literature:</p> <ul> <li>Greulich F, Bielefeld KA, Scheundel R
                  , Mechtidou A, Strickland B, Uhlenhaut NH, 2021, Research article, Enhancer
                  RNA Expression in Response to Glucocorticoid Treatment in Murine Macrophages
                  ., Cells;11(1):28</li> <li>Greulich F, Wierer M, Mechtidou A, Gonzalez-Garc
                  ia O, Uhlenhaut NH, 2021, Research article, The glucocorticoid receptor recr
                  uits the COMPASS complex to regulate inflammatory transcription at macrophag
                  e enhancers., Cell Rep.;34(6):108742</li> <li>Strickland BA, Ansari SA, Dan
                  toft W, Uhlenhaut NH., 2022, Review, How to tame your genes: mechanisms of i
                  nflammatory gene repression by glucocorticoids. FEBS Lett. Epub ahead of pri
                  nt</li> <li>Cao Z, Grima R., 2020, Analytical distributions for detailed mo
                  dels of stochastic gene expression in eukaryotic cells. Proceedings of the N
                  ational Academy of Sciences 117.9: 4682-4692</li> <li>Jiang Q, Fu X, Yan S,
                   Li R, Du W, Cao Z, Qian F and Grima R, 2021. Neural network aided approxima
                  tion and parameter inference of non-Markovian models of gene expression. Nat
                  ure communications, 12(1), pp.1-12</li> </ul>
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EpiCrossBorders Projects