skip to content

Department of Zoology

 

Biography

Raised in the fenlands of Northern Germany, I emigrated to London, where I read Genetics at University College London; then embarked on a PhD in Cambridge with Prof. Michael Bate on the development of the locomotor network of Drosophila melanogaster. Following an interlude of national service, working as a home care nurse in Berlin, I returned to Cambridge, initially as a postdoctoral research fellow. In 2002 I was awarded a Royal Society University Research Fellowship, which allowed me to start an independent research group, followed in 2010 by a lectureship position and, more recently, promotion to the position of Reader (Associate Professor). In addition to early instrumental funding by the Royal Society, our research has consistenly been funded by the Wellcome Trust and the Biotechnology and Biological Sciences Research Council (BBSRC)

I have been supporting postgraduate education within the Department as Deputy Director for Postgraduate Education, and, at School level been developing postgraduate strategy as Deputy Head of School - Postgraduate Strategy.

Research

We are interested in understanding how nervous systems develop and become functional. As a model system we use the locomotor network of the Drosophila embryo and larva, as this allows us to work with identified connecting nerve cells to which we can return time and again. Using state of the art genetics, imaging, electrophysiology and behavioural analysis we are investigating several interlinked questions:

Connectivity: Our early work made seminal contriutions to understanding the functional architecture of the locomotor system; in that motorneuron connectivity within the nerve cord reflects the map of body wall muscles. In collaboration with the group of Albert Cardona, MRC-LMB and Department of PDN, we contribute to investigating the detailed network connectivity. 

Critical periods of nervous system development: Nervous systems, as many biological systems, manifest considerable levels of variability. How can networks reliably generate specific behaviours in the face of this inherent variability? As nervous systems become functional, the neurons within a given network need to adjust to each other, so that they can work well together within a network to generate appropriate behavioural outputs. These early tuning phases are called 'critical periods' because errors that occur during such a critical period usually cause network instabilty (leading to seizures and other network malfunction). Importantly, such critical period induced errors remain locked in, for reasons not yet understood. In collaboration with Dr Timothy O'Leary, Department of Engineering, and Prof. Richard Baines, University of Manchester, we are investigating: a) changes that occur in the network during a critical period; b) what properties of nerve cells are specified during a critical period (e.g. excitability or homeostatic setpoint); c) why it is that later plasticity mechanisms cannot correct for critical period-induced errors. Funded by EMBO, we are studying mechanisms by which transient embryonic experiences cause lasting change in gene expression and thus in neuronal properties.

Adjustment of connections and structural homeostasis: We discovered that nerve cells adjust their structure, e.g. the size of their dendritic arbors, so as to regulate in a homeostatic fashion the number of input synapses they receive. Structural changes are important tools that networks use to adjust themselves, as they assemble, mature and grow. 

Mechanisms regulating change - metabolic reactive oxidative species as regulators of cellular 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 synaptic terminal growth and synaptic connectivity during normal development and under conditions of oxidative stress. 

Publications

Key publications: 

Dhawan S, Myers P, Bailey DMD, Ostrovsky AD, Evers JF, Landgraf M. (2021). Reactive Oxygen Species Mediate Activity-Regulated Dendritic Plasticity Through NADPH Oxidase and Aquaporin Regulation. Front Cell Neurosci. 2021; 15: 641802. DOI: 10.3389/fncel.2021.641802.

Valdes-Aleman J, Fetter RD, Sales EC, Heckman EL, Venkatasubramanian L, Doe CQ, Landgraf M, Cardona A, Zlatic M. (2021). Comparative Connectomics Reveals How Partner Identity, Location, and Activity Specify Synaptic Connectivity in Drosophila. Neuron. 2021 Jan 6; 109(1): 105–122.e7. DOI 10.1016/j.neuron.2020.10.004.

Oswald MCW, Garnham N, Sweeney ST 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, Giachello, CNGMorarach K, Baines RA, Sweeney ST and Landgraf M. (2018). Reactive Oxygen Species Regulate Activity-Dependent Neuronal Structural Plasticity.  eLife, 7. DOI: 10.7554/eLife.39393.

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 Bate M. (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.

Supervisions

Research supervision: 

We provide a supportive, nurturing environment to both undergraduate and postgraduate students, almost all of whom have continued in research and research-related professions. If you are interested in the questions we are asking and are keen to pursue a career in research, get in touch.

Professor of Developmental Neurobiology

Contact Details

Rooms B22 (Office); B12 & B24 (labs)
01223 (7)69348
Accepting applications for PhD students.

Affiliations

Person keywords: 
Developmental Biology
Imaging technologies
Cellular and Molecular Neuroscience
Plasticity mechanisms
Reactive oxygen species
Drosophila genetics