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Dr Matthias Landgraf

Dr Matthias Landgraf

Lecturer

Matthias Landgraf is accepting applications for PhD students.

Rooms B22/B12/B24
Office Phone: 01223 (7)69348 or (3)36681 or (3)36635

Research Interests

We are interested in understanding how neural networks are specified and assembled. We focus on the locomotor network of the Drosophila embryo and larva. This model system allows us to work with identified connecting nerve cells to which we can return time and again. Using state of the art genetics and imaging we are investigating several interlinked questions:

Specification of network components: Neuroblasts and the lineages that these generate are the fundamental developmental modules of the nervous system. We would like to understand if there is a developmental logic by which neural progenitors produce distinct network elements.

Connectivity: At the output level, the motor system has a straightforward organizational logic in that motoneurons position their dendrites so that these form a neural ‘myotopic’ map of the body wall musculature. In collaboration with the group of Albert Cardona, HHMI Janelia Farm Research Campus, we are establishing the neuronal network upstream of this myotopic map of motoneuron dendrites. We studying mechanisms that underlie the formation of ordered connectivity in the developing locomotor network, for example by targeting presynaptic axons terminals and postsynaptic dendrites to specific regions of the nervous system. In collaboration with Jan Felix Evers, Centre for Organismal Studies, Heidelberg, we have developed genetic tools that allow us to study synapse formation between identified nerve cells in the central nervous system.

Adjustment of connections and structural homeostasis: Nervous systems manifest considerable levels of variability. How can networks reliably generate specific outputs in the face or naturally occurring variability? We discovered that nerve cells adjust the size of their dendritic arbors so as to regulate the number of input synapses they receive. We are studying mechanisms, including structural homeostasis of dendrites, which networks use to adjust as they assemble and mature.

Oxidative stress and synaptic growth: High levels of reactive oxygen species are a hallmark of many neurodegenerative conditions, leading to damage of cell membranes and cytoskeletal elements, and, eventually cell death. However, at low levels, the same molecules can act as important messengers. In collaboration with Sean Sweeney, University of York, we are investigating how reactive oxygen species regulate central and peripheral synapse development and function during normal development and under conditions of oxidative stress. 

Keywords

  • Neuroanatomy
  • Fluorescence Light microscopy
  • Cellular and Molecular Neuroscience
  • Drosophila genetics
  • Imaging technologies

Key Publications

Oswald, M. C. W., Garnham, N., Sweeney, S. T. and Landgraf, M. (2018). Regulation of neuronal development and function by ROS. FEBS Lett. DOI: 10.1002/1873-3468.12972.

Oswald MCW, Brooks PS, Zwart MF, Mukherjee A, West RJH, Morarach K, Sweeney ST and Landgraf M. (2017). Reactive Oxygen Species Regulate Activity-Dependent Neuronal Structural Plasticity.  bioRxiv 081968.  DOI: dx.doi.org/10.1101/081968 

Zwart MF, Pulver SR, Truman JW, Fushiki A, Fetter, RD, Cardona A, Landgraf M. (2016). Selective Inhibition Mediates the Sequential Recruitment of Motor Pools. Neuron 91(3):615-628.  DOI: 10.1016/j.neuron.2016.06.031.  

Peco E, Davla S, Camp D, Stacey S, Landgraf M, van Meyel D. (2016). Drosophila astrocytes cover specific territories of CNS neuropil and are instructed to differentiate by Prospero, a key effector of Notch. Development. 143(7):1170-1181.   DOI: 10.1242/dev.133165.    

Couton L, Mauss AS, Yunusov T, Diegelmann S, Evers JF, Landgraf M (2015). Development of connectivity in a motoneuronal network in Drosophila larvae. Curr Biol 25: 568–576, 2015. DOI: 10.1016/j.cub.2014.12.056.  (see also Dispatch by Sternberg JR, Wyart C. Neuronal wiring: linking dendrite placement to synapse formation. Curr Biol 25: R190–1, 2015.)

Diao F, Ironfield H, Luan H, Diao F, Shropshire WC, Ewer J, Marr E, Potter CJ, Landgraf M, White BH (2015). Plug-and-Play Genetic Access to Drosophila Cell Types using Exchangeable Exon Cassettes. Cell Rep 10: 1410–1421, 2015. DOI:  10.1016/j.celrep.2015.01.059

Zwart MF, Randlett O, Evers JF, Landgraf M. Dendritic growth gated by a steroid hormone receptor underlies increases in activity in the developing Drosophila locomotor system (2013). Proc Natl Acad Sci U S A (September 16, 2013). DOI: 10.1073/pnas.1311711110.

Mauss A, Tripodi M, Evers JF, Landgraf M (2009) Midline signalling systems direct the formation of a neural map by dendritic targeting in the Drosophila motor system. PLoS Biol 7(9):e1000200.  DOI:  10.1371/journal.pbio.1000200

Tripodi M, Evers JF, Mauss A, Bate M, Landgraf M (2008) Structural homeostasis: compensatory adjustments of dendritic arbor geometry in response to variations of synaptic inputPLoS Biol 6(10):e260. DOI: 10.1371/journal.pbio.0060260.

Other Publications

Heckscher ES, Zarin AA, Faumont S, Clark MQ, Manning L, Fushiki A, Schneider-Mizell CM, Fetter RD, Truman JW, Zwart MF, Landgraf M, Cardona A, Lockery SR, Doe CQ (2015). Even-Skipped(+) Interneurons Are Core Components of a Sensorimotor Circuit that Maintains Left-Right Symmetric Muscle Contraction Amplitude. Neuron. doi: 10.1016/j.neuron.2015.09.009.

Bujdoso R, Landgraf M, Jackson WS, Thackray AM (2015). Prion-induced neurotoxicity: Possible role for cell cycle activity and DNA damage response. World J Virol 4: 188–197.

Lowe N, Rees JS, Roote J, Ryder E, Armean IM, Johnson G, Drummond E, Spriggs H, Drummond J, Magbanua JP, Naylor H, Sanson B, Bastock R, Huelsmann S, Trovisco V, Landgraf M, Knowles-Barley S, Armstrong JD, White-Cooper H, Hansen C, Phillips RG, UK Drosophila Protein Trap Screening Consortium, Lilley KS, Russell S, St Johnston D (2014). Analysis of the expression patterns, subcellular localisations and interaction partners of Drosophila proteins using a pigP protein trap library. Development 141: 3994–4005.

Lu CS, Zhai B, Mauss A, Landgraf M, Gygi S, Van Vactor D (2014). MicroRNA-8 promotes robust motor axon targeting by coordinate regulation of cell adhesion molecules during synapse development. Philos Trans R Soc Lond, B, Biol Sci 369.

Singh AP, Das RN, Rao G, Aggarwal A, Diegelmann S, Evers JF, Karandikar H, Landgraf M, Rodrigues V, VijayRaghavan K (2013). Sensory neuron-derived eph regulates glomerular arbors and modulatory function of a central serotonergic neuron. PLoS Genet 9: e1003452.

Thackray AM, Muhammad F, Zhang C, Di Y, Jahn TR, Landgraf M, Crowther DC, Evers JF, Bujdoso R (2012). Ovine PrP transgenic Drosophila show reduced locomotor activity and decreased survival. Biochem J 444: 487–495.

Nicolaï, L.J., Ramaekers, A., Raemaekers, T., Drozdzecki, A., Mauss, A.S., Yan, J., Landgraf, M., Annaert, W., Hassan, B.A., (2010). Genetically encoded dendritic marker sheds light on neuronal connectivity in Drosophila. Proc Natl Acad Sci USA 107, 20553-20558.

Roy, B., Singh, A.P., Shetty, C., Chaudhary, V., North, A., Landgraf, M., Vijayraghavan, K., Rodrigues, V.  (2007).  Metamorphosis of an identified serotonergic neuron in the Drosophila olfactory system. Neural Development 2, 20.

Fujioka, M., Lear B.C., Landgraf, M., Yusibova, G.L., Zhou, J., Riley, K.M., Patel, N.H.,and Jaynes, J.B. (2003) Even-skipped, acting as a repressor, regulates axonal projections in Drosophila. Development 130:5385-5400.

Ruiz-Gómez, M., Coutts, N., Suster, M.L., Landgraf, M. and BateM. (2002) myoblasts incompetent encodes a zinc finger transcription factor required to specify fusion competent myoblasts in Drosophila. Development 129:133-141.

San Martin, B., Ruiz-Gomez, M., Landgraf, M., and Bate, M. (2001) A distinct set of founders and fusion-competent myoblasts make visceral muscles in the Drosophila embryo. Development 128:3331-3338.

Hartmann, C., Landgraf, M., Bate, M. and Jäckle, H. (1997) The Krüppel target gene knockout participates in the proper innervation of a specific set of Drosophila larval muscles. EMBO J. 16:5299-5309.

Prokop, A., Landgraf, M., Rushton, E., Broadie, K. and Bate, M. (1996) Presynaptic development at the Drosophila neuromuscular junction:assembly and localisation of presynaptic active zones. Neuron 17:617-626.