Bergami, Matteo - C 02

Maintenance of a functional mitochondrial network in neurons depends upon highly regulated mitochondrial transport dynamics. Mutations in genes encoding mitochondrial transport machinery proteins lead to a spectrum neuropathies/encephalopathies and other severe neurological symptoms in humans. Among 

recently identified mutations are loss-of-function and other pathogenic variants of the TRAK1 gene, which associate with congenital hyperekplexia/myoclonus. Despite the proposed role for TRAK1, the precise molecular mechanisms underlying its roles in seizure susceptibility remain poorly understood. Using new genetic tools, in this project we aim to elucidate the mechanisms by which TRAK1 disruption affects neuronal circuit excitability.

Understanding the molecular underpinnings by which TRAK1 mutations cause seizure phenotypes can inform targeted therapeutic interventions. This proposal aims to elucidate the role of TRAK1-regulated axonal mitochondrial trafficking in synapse function, and the consequences of its disruption for the pathogenesis of epilepsy, with the ultimate goal of identifying novel strategies to mitigate seizure activity in patients carrying TRAK1 variants.

• Mouse genetics
• Viral approaches
• Advanced light and electron microscopy techniques
• Omics approaches
• Electrophysiology

Kochan, SMV, Cepero Malo, M, Jevtic, M, Jahn-Kelleter, HM, Wani, GA, Ndoci, K, Perez-Revuelta, L, Gaedke, F, Schäffner, I, Chichung-Lie, D, Schauss, A, and Bergami, M. Enhanced mitochondrial fusion during a critical period of synaptic plasticity in adult-born neurons. Neuron (2024); 112,1997-2014.e6. Doi: 10.1016/j.neuron.2024.03.013.

Wani, GA, Sprenger, HG, Ndoci, K, Chandragiri, S, Acton, JR, Schatton, D, Kochan, SMV, Sakthivelu, V, Jevtic, M, Seeger, JM, Müller, S, Giavalisco, P, Rugarli, EI, Motori, E, Langer, T, Bergami, M. Metabolic control of adult neural stem cell self-renewal by the mitochondrial protease YME1L. Cell Reports (2022); 38, 110370. Doi:10.1016/j.celrep.2022.110370.

For more research information, please check Bergami Lab. 

• Center for Molecular Medicine Cologne (CMMC)
• CECAD Research Center Cologne
• CRC 1218: Role of mitochondrial dynamics in neuronal synapse and circuit remodelling
• CRC 1451