Functional Genetics of Neurodegeneration and Neurological Disorders Working Group

Unsolicited applications for scientific PhD positions (m/f/d) and postdoctoral positions (m/f/d) are always welcome!

The same applies to applications for theses in Bachelor (B.Sc) and Master (M.Sc.).

All applications should include a meaningful curriculum vitae in tabular form, a transcript of the modules completed to date or proof of the degrees completed to date, as well as a brief description of professional aptitude and personal motivation. Further attachments can be added optionally.

The Functional Genetics of Neurodegeneration and Neurological Disorders working group, led by Dr. Hans Zempel, PhD, is researching the pathological mechanisms of neurodegenerative and rare genetic neurological diseases. We are working to identify and characterize the factors that influence neuron and synaptic function. Rare genetic diseases often provide information on the development and treatment of age-related diseases, including those of a non-genetic nature - such as Alzheimer’s type dementia.

With the additional support of the CMMC, we use state-of-the-art microscopy, cell biology, genetic and biochemical methods to identify and characterize genetic and non-genetic factors of neurodegeneration of the central and peripheral nervous system.

Our research focuses on the cellular and molecular mechanisms and therapy of

  • Alzheimer’s type dementia and applied related tauopathies, such as Frontotemporal dementias (Pick's disease, corticobasal degeneration, progressive supranuclear paralysis)
  • Mitochondriopathies, such as polymerase gamma mutations
  • Neurological diseases caused by cytoskeletal disorders, cellular transport disorders or neuronal migration disorders (hereditary spastic paraplegia (HSP), lissencephalopathies)
  • 2-hydroxyglutarate aciduria and related syndromes
  • Lysosomal storage disorders
  • Neuronal cell polarity

We welcome initiatives for scientific collaboration and ideas for the treatment of neurodegenerative diseases.

External funding

  • Else-Kröner-Fresenius-Stiftung
  • Jürgen-Manchot-Stiftung
  • Studienstiftung des deutschen Volkes
  • Köln Fortune
Selected publications

Schützmann MP*, Hasecke F*, Bachmann S, Zielinski M, Hänsch S, Schröder GF, Zempel H, Hoyer W. (* indicates shared first-authorship)
Endo-lysosomal Aβ concentration and pH trigger formation of Aβ oligomers that potently induce Tau missorting.
Nat Commun. 2021 Jul 30;12(1):4634. doi: 10.1038/s41467-021-24900-4.
PubMed PMID: 34330900

Bachmann S, Bell M, Klimek J, Zempel H.
Differential Effects of the Six Human TAU Isoforms: Somatic Retention of 2N-TAU and Increased Microtubule Number Induced by 4R-TAU.
Front Neurosci. 2021 May 25;15:643115. doi: 10.3389/fnins.2021.643115.
PubMed PMID: 34113229

Bell M, Zempel H.
SH-SY5Y-derived neurons: a human neuronal model system for investigating TAU sorting and neuronal subtype-specific TAU vulnerability.
Rev Neurosci. 2021 Apr 16. doi: 10.1515/revneuro-2020-0152. Epub ahead of print.
PubMed PMID: 33866701

Bell M, Bachmann S, Klimek J, Langerscheidt F, Zempel H.
Axonal TAU Sorting Requires the C-terminus of TAU but is Independent of ANKG and TRIM46 Enrichment at the AIS.
Neuroscience. 2021 May 1;461:155-171. doi: 10.1016/j.neuroscience.2021.01.041. Epub 2021 Feb 6.
PubMed PMID: 33556457

Bachmann S, Linde J, Bell M, Spehr M, Zempel H, Zimmer-Bensch G.
DNA Methyltransferase 1 (DNMT1) Shapes Neuronal Activity of Human iPSC-Derived Glutamatergic Cortical Neurons.
Int J Mol Sci. 2021 Feb 18;22(4):2034. doi: 10.3390/ijms22042034.
PubMed PMID: 33670788

Zempel H, Mandelkow E.
Mechanisms of Axonal Sorting of Tau and Influence of the Axon Initial Segment on Tau Cell Polarity.
Adv Exp Med Biol. 2019;1184:69-77. doi: 10.1007/978-981-32-9358-8_6.
PubMed PMID: 32096029

Zempel H, Dennissen FJA, Kumar Y, Luedtke J, Biernat J, Mandelkow EM, Mandelkow E.
Axodendritic sorting and pathological missorting of Tau are isoform-specific and determined by axon initial segment architecture.
J Biol Chem. 2017 Jul 21;292(29):12192-12207. doi: 10.1074/jbc.M117.784702. Epub 2017 May 23.<
PubMed PMID: 28536263

Zempel H, Mandelkow E.
Lost after translation: missorting of Tau protein and consequences for Alzheimer disease.
Trends Neurosci. 2014 Dec;37(12):721-32. doi: 10.1016/j.tins.2014.08.004. Epub 2014 Sep 12. Review.
PubMed PMID: 25223701

Zempel H, Luedtke J, Kumar Y, Biernat J, Dawson H, Mandelkow E, Mandelkow EM.
Amyloid-β oligomers induce synaptic damage via Tau-dependent microtubule severing by TTLL6 and spastin.
EMBO J. 2013 Nov 13;32(22):2920-37. doi: 10.1038/emboj.2013.207. Epub 2013 Sep 24.
PubMed PMID: 24065130

Zempel H, Thies E, Mandelkow E, Mandelkow EM.
Abeta oligomers cause localized Ca(2+) elevation, missorting of endogenous Tau into dendrites, Tau phosphorylation, and destruction of microtubules and spines.
J Neurosci. 2010 Sep 8;30(36):11938-50. doi: 10.1523/JNEUROSCI.2357-10.2010. Erratum in: J Neurosci. 2012 Apr 25;32(17):6052.
PubMed PMID: 2082665

Curriculum Vitae
Academic education
08/2018 Medical Approbation, University of Bonn & Medical thesis, magna cum laude (0,5)
2015–2018 Clinical Medicine, Student, University Bonn & Postdoc (50%), DZNE, Bonn
12/2013 PhD Thesis, Biochemistry, summa cum laude (1,0*), Hamburg University & Max-Planck Groups for Structural Molecular Biology
2006–2008 Clinical Medicine, Medical and Dental University Tokyo, Japan
2005–2006 Biophysics & Genetics, Kyoto University, Japan
2002–2006 Biochemistry & Biophysics, MSc in Biochemistry, Berlin University (FU) & Charité, Berlin, Germany
2000–2002 Abitur, with honors, top of class (grade 1,2) Gymnasium Oberasbach b. Nürnberg
1999–2000 High-School Diploma, with honors, Rancocas Valley High School, NJ, USA
Clinical course / work experience 
Since 09/2018 Principal Investigator & Medical Doctor Institute for Human Genetics, University Clinic Cologne
04/2018–08/2018 Chief Scientific Officer (Start-up company, EF incubator) MedXact technology ltd. (now Juniper Medical Computing), Berlin/London
2017–2018 Clinical Rotations: Neurology (Univ. Liège, Belgium), Surgery (Univ. Würzburg, Germany), Internal Medicine (Univ. La Laguna, Spain) 
2010–2017 PhD & PostDoc by German Center for Neurodegenerative Diseases (DZNE), Bonn & Max-Planck Group for Struct. & Mol. Biology, Hamburg

Team

Sarah Bachmann, M.Sc., PhD candidate
Michael Bell, M.Sc., PhD candidate
Helen Breuer, cand med, MD candidate
Cagla Cakmak, M.Sc., PhD candidate
Jana Chudobova, MD candidate
MhD Aghyad Al Kabbani, MSc, PhD candidate
Lena Kluge, B.Sc., master´s candidate
Jennifer Klimek, biological-technical assistant
Felix Langerscheidt, B.Sc., master´s candidate
Thilo Löhr, B.Sc. candidate

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