Prof Matthias Landgraf
- Professor of Developmental Neurobiology
Contact
Connect
Location
- Rooms B22 (Office); B12 & B24 (labs)
About
I am group leader of the Neural Network Development Group and co-leader, with Greg Jefferis and Marta Zlatic of the Drosophila Connectomics Group.
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 locomotor networks, using the fruit fly, Drosophila melanogaster, as an experimental model. Following an interlude of national service, as a home care nurse in Berlin, I returned to Cambridge as a postdoctoral research fellow. A Royal Society University Research Fellowship allowed me to start my independent research group in 2002, followed in 2010 by a lectureship position and in 2023 promotion to Professor (of Developmental Neurobiology).
In addition to early instrumental funding by the Royal Society, our research has consistently been funded by the Wellcome Trust and the Biotechnology and Biological Sciences Research Council (BBSRC).
I have a passion for postgraduate training, education and support, and for equity within and equitable access into postgraduate education. As Deputy Head of School - Postgraduate Strategy (2020-2026) I have been championing widening participation across the Faculty/School within the wider University in many ways, including: the creation of a dedicated summer placement scheme (Experience Postgrad Life Sciences), and, with the help of many wonderful colleagues, of thematic masters/MPhil courses with dedicated widening participation bursaries.
Research
We are interested in understanding how nervous systems develop and how function emerges. One of the central questions is: How does nature deal with what it cannot predict, such as changes in (seasonal/global) temperature. As a model system we use the locomotor network of the Drosophila (fruit fly) embryo and larva, as this allows us to work with identified connecting nerve cells to which we can return time and again. As experimental approaches we use state of the art genetics, imaging, electrophysiology and behavioural analysis.
Critical periods of nervous system development: Nervous systems, like many biological systems, manifest appreciable levels of variability. How can networks reliably generate robust behaviours in the face of inherent cell-to-cell variability? When neural networks become functional, their constituent cells need to adjust to each other, so that they can work well together in order to generate appropriate behavioural outputs. These tuning phases are called 'critical periods' because perturbations during a critical period usually cause network instability (leading to seizures and other network malfunction). Importantly, critical period-induced errors persist longterm. This presents another unresolved mystery, namely how is it that such errors cannot be corrected by the many plasticity mechanisms that nerve cells have at their disposal? For example, a transient 2-hour heat stress experience during the embryonic critical period causes lasting maladjustment of the nervous systems. This manifests as altered behaviour and inherent network instability, which causes seizure susceptibility to seizures.
In collaboration with Prof. Richard Baines, University of Manchester, we have been investigating (Wellcome Trust and BBSRC funded) the changes that critical period perturbations cause in the network (e.g. structural) and the properties of nerve cells (e.g. excitability). One line of thought is that critical periods define homeostatic setpoints. A change in homeostatic setpoint would immediately explain why a critical period-induced change in properties cannot be later 'corrected' by other plasticity mechanisms.
Funded by EMBO, we have discovered that mitochondrial (Reactive Oxygen Species) and metabolic signals (HIF-1alpha) instruct lasting changes in cellular metabolism and gene expression. Now, with renewed BBSRC funding, we are exploring the underlying mechanisms that define the developmental window of the critical period, and how such changes in cellular properties are maintained well into late life.
Key publications:
Sobrido-Cameán D, Coulson B, Miller M, Oswald MCW, Pettini T, Bailey DMD, Baines RA, Landgraf M. (2025) Mitochondrial ROS and HIF-1α signaling mediate synaptic plasticity in the critical period. PLoS Biol. 23(8):e3003338. doi: 10.1371/journal.pbio.3003338.
Corke J, Huertas-Radi M, Landgraf M, Baines RA. (2025). Maturation of GABAergic signalling times the opening of a critical period in Drosophila melanogaster. Sci Rep. 15(1):40285. doi: 10.1038/s41598-025-24116-2.
Hunter I, Coulson B, Pettini T, Davies JJ, Parkin J, Landgraf M, Baines RA. (2024). Balance of activity during a critical period tunes a developing network. Elife. 12:RP91599. doi: 10.7554/eLife.91599.
Sobrido-Cameán D, Oswald MCW, Bailey DMD, Mukherjee A, Landgraf M. (2023). Activity-regulated growth of motoneurons at the neuromuscular junction is mediated by NADPH oxidases. Front Cell Neurosci. 16:1106593. doi: 10.3389/fncel.2022.1106593.
Giachello CNG, Hunter I, Pettini T, Coulson B, Knüfer A, Cachero S, Winding M, Arzan Zarin A, Kohsaka H, Fan YN, Nose A, Landgraf M, Baines RA. (2022). Electrophysiological Validation of Monosynaptic Connectivity between Premotor Interneurons and the aCC Motoneuron in the Drosophila Larval CNS. J Neurosci. 42(35):6724-6738. doi: 10.1523/JNEUROSCI.2463-21.2022.
Giachello CNG, Fan YN, Landgraf M, Baines RA. (2021). Nitric oxide mediates activity-dependent change to synaptic excitation during a critical period in Drosophila. Sci Rep. 11:20286. doi: 10.1038/s41598-021-99868-8.
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.
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.
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.)
Teaching and supervision
Teaching:
My teaching focuses on different aspects of nervous system development - from growth cones & axon pathfinding to the formation of neural networks and critical period plasticity. I enjoy interactive seminars at Masters/MPhil level, including on PhD applications & interview preparation.
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. Everyone thinks and learns differently. That's fun and creative. If you are interested in what we study and would like to experience lab-based research, get in touch.