Lukas J. Neukomm, Ph.D.

SNSF Assistant Professor, Department of Fundamental Neurosciences, DNF University of Lausanne, UniL

Lukas J. Neukomm, Ph.D.

SNSF Assistant Professor, Department of Fundamental Neurosciences, DNF University of Lausanne, UniL

Biography

Dr. Neukomm received his MSc at ETH Zürich (Switzerland) in 2003, where he studied cell biology, biochemistry and cellular energetics. He then moved to the University of Zürich, where he completed his PhD in Molecular Biology in 2008, with a focus on how sick, unhealthy cells are either tolerated, or removed by the surrounding tissue in the roundworm C. elegans. For his PostDoctoral training, he moved to the Neurobiology Department / Howard Hughes Medical Institute at University of Massachusetts Medical School (USA), where he specialized in axon degeneration in the fruit fly D. melanogaster. He is a recipient of an Assistant Professor Career Award, which is funded by the Swiss National Science Foundation (SNSF), and started his own laboratory at the Department of Fundamental Neurosciences at University of Lausanne (Switzerland) in 2018.

Dr. Neukomm is broadly interested in degenerative mechanisms of neurons and their long axons. During his PostDoctoral training, he established a genetic approach that allows him to readily observe and manipulate individual sensory and motor neurons and their long axons in Drosophila. This approach allowed him to identify genes which are essential for injury-induced axon degeneration including axundead (axed). Currently, his laboratory is focusing on better understanding the molecular mechanisms underlying axon death signaling in severed axons. His laboratory also investigates how neurons execute their own degeneration. Two models are used to provide insights into the mechanisms underlying neurodegeneration. How do low levels of the essential coenzyme and cofactor Nicotinamide Adenine Dinucleotide (NAD+) translate into neurodegeneration, and how do impaired synapses trigger the degeneration of whole neurons.

Axon death from a fly’s perspective

Axon degeneration is a shared feature in neurodegenerative disease, and when nervous systems are challenged by mechanical or chemical forces. Yet our understanding of the molecular mechanisms underlying axon degeneration remains fairly limited. Injury-induced axon degeneration serves as a simple model to study how severed axons execute their own disassembly. Discovered by and named after Augustus Waller in 1850, Wallerian degeneration is an umbrella term that comprises of two distinct, molecularly separable processes. First, after axonal injury, axons separated from their cell bodies actively execute their own self-destruction (axon death) through an evolutionarily conserved axon death signaling cascade within one day after injury. Second, surrounding glia and specialized phagocytes engage and clear the resulting axonal debris within three to five days. Over recent years, an evolutionarily conserved axon death signaling cascade has been identified from flies to mammals, which is required for the separated axon to degenerate after injury. Conversely, attenuated axon death signaling results in severed axons and their synapses which remain morphologically and functionally preserved for weeks to months.

We use Drosophila and its powerful genetics to study axon death signaling. A recently established novel approach in the wing will be presented that allows for the observation and manipulation with the resolution of single, individual axons of sensory neurons. It led to the discovery and characterization of axundead (axed), which is a novel, essential axon death gene. We’ll share our most recent unpublished insights related to axon death signaling, with a particular focus on Axed.

Axon death signaling is not only activated following injury, it is also engaged in a broad range of neurodegenerative conditions. Defining the molecular machinery that executes axon death could therefore provide exciting targets for therapeutic intervention both in neural injury and in neurodegenerative disease.

All sessions by Lukas J. Neukomm, Ph.D.