Neurons, synapses, and the proteins required for their function are critical to the biology and behaviour of animals, but little is known about how they first evolved. In neurons, the transmission of chemical signals (called neuropeptides or neurotransmitters) from the presynapse to the postsynapse requires distinct sets of pre- and postsynaptic protein networks. Understanding when the proteins required for synaptic activity first evolved and how they functioned in the first animals promises to illuminate evolutionary processes underlying the origin of neurons. We are particularly interested in:

• The origin and functional evolution of synaptic proteins
• Co-option of these proteins into ancient synaptic scaffolds
• Evolution of the first neuron-like cell type in animals

We use a comparative approach and work with choanoflagellates, the closest unicellular relatives of animals, sponges, early branching animals with no synapses and neurons, and ctenophores, early branching animals with synapses and neurons, as model organisms. We aim to understand when the proteins required for synaptic activity first evolved, how they functioned at a molecular level and which combinations of synaptic proteins resulted in the origin of the synapse. Our approach is to use a variety of techniques, ranging from comparative genomics, immunofluorescence and electron microscopy, current state-of-the-art biochemical methods to X-ray crystallography to study synaptic protein homologs in choanoflagellates, sponges and ctenophores. Through our work we will be able to reconstruct the evolutionary history of these proteins and understand the evolution of the first synapses and neurons.

Academic article

• Benvenuto, Giovanna; Leone, Serena; Astoricchio, Emanuele et al. (2024). Evolution of the ribbon-like organization of the Golgi apparatus in animal cells. (external link)
• Soto Angel, Joan-Josep; Nordmann, Eva-Lena; Sturm, Daniela et al. (2024). Stable Laboratory Culture System for the Ctenophore Mnemiopsis leidyi. (external link)
• Hake, K.H.; West, P.T.; McDonald, K. et al. (2024). A large colonial choanoflagellate from Mono Lake harbors live bacteria. (external link)
• Kollmar, Martin; Welz, Tobias; Ravi, Aishwarya et al. (2024). Actomyosin organelle functions of SPIRE actin nucleators precede animal evolution. (external link)
• Soto Angel, Joan-Josep; Burkhardt, Pawel (2024). Reverse development in the ctenophore Mnemiopsis leidyi. (external link)
• Burkhardt, Pawel; Colgren, Jeffrey John; Medhus, Astrid et al. (2023). Syncytial nerve net in a ctenophore adds insights on the evolution of nervous systems. (external link)
• Gahan, James Michael; Kouzel, Ivan; Jansen, Kamilla Ormevik et al. (2022). Histone demethylase Lsd1 is required for the differentiation of neural cells in Nematostella vectensis. (external link)
• Colgren, Jeffrey John; Burkhardt, Pawel (2022). The premetazoan ancestry of the synaptic toolkit and appearance of first neurons. (external link)
• Musser, Jacob M.; Schippers, Klaske J.; Nickel, Michael et al. (2021). Profiling cellular diversity in sponges informs animal cell type and nervous system evolution. (external link)
• Göhde, Ronja Alica Angelika; Naumann, Benjamin; Laundon, Davis et al. (2021). Choanoflagellates and the ancestry of neurosecretory vesicles. (external link)
• Sachkova, Mariia; Nordmann, Eva-Lena; Angel, Joan-Josep Soto et al. (2021). Neuropeptide repertoire and 3D anatomy of the ctenophore nervous system. (external link)
• Laundon, Davis; Larson, Ben T; McDonald, Kent et al. (2019). The architecture of cell differentiation in choanoflagellates and sponge choanocytes. (external link)
• Naumann, Benjamin; Burkhardt, Pawel (2019). Spatial cell disparity in the colonial choanoflagellate salpingoeca rosetta. (external link)

Letter to the editor

• Soto Angel, Joan-Josep; Jaspers, C.; Hosia, Aino Laila Johanna et al. (2023). Are we there yet to eliminate the terms larva, metamorphosis, and dissogeny from the ctenophore literature?. (external link)

Academic literature review

• Burkhardt, Pawel; Jékely, Gáspár (2021). Evolution of synapses and neurotransmitter systems: The divide-and-conquer model for early neural cell-type evolution. (external link)
• Sachkova, Maria; Burkhardt, Pawel (2019). Exciting times to study the identity and evolution of cell types. (external link)

See a complete overview of publications in Cristin.

• Soto Angel JJ, Nordmann EL, Sturm D, Sachkova M, Pang K, Burkhardt P (2024) Stable laboratory culture system for the ctenophore Mnemiopsis leidyi. Methods in Molecular Biology 2757: 123–145.

• Benvenuto G, Leone S, Astoricchio E, Bormke S, Jasek S, D'Aniello E, Kittelmann M, McDonald K, Hartenstein V, Baena V, Escriva H, Bertand S, Schierwater B, Burkhardt P, Ruiz-Trillo I, Jekely G, Ullrich-Luter J, Luter C, D'Aniello S, Arnone MI, Ferraro F (2024) Evolution of the ribbon-like organization of the Golgi apparatus in animal cells. Cell Reports 43: 113791.

• Colgren J, Burkhardt P (2023) Evolution: Was Nuclear to Cytoplasmic Ratio a Key Factor in the Origin of Animal Multicellularity? Current Biology 33, 298-300.

• Burkhardt P, Colgren J, Medhus A, Digel L, Naumann B, Soto Angel JJ, Nordmann EL, Sachkova MY, Kittelmann M (2023) Syncytial nerve net in a ctenophore adds insights on the evolution of nervous systems. Science 376 (6642): 293-297.

• Soto Angel JJ, Jaspers C, Hosia A, Majaneva S, Martell L, Burkhardt P (2023) Are we there yet to eliminate the terms larva, metamorphosis and dissogeny from the ctenophore literature? Proceedings of the National Academy of Sciences 120 (4): e2218317120

• Colgren J, Burkhardt P (2022) The premetazoan ancestry of the synaptic toolkit and appearance of first neurons. Essays in Biochemistry 66 (6): 781–795.

• Burkhardt P (2022) Ctenophores and the evolutionary origin(s) of neurons. Trends in Neurosciences 45 (12): 878-880.

• Gahan JM, Kouzel IU, Jansen KO, Burkhardt P, Rentzsch F (2022) Histone demethylase Lsd1 is required for the differentiation of neural cells in Nematostella vectensis. Nature Communications 13 (1):465.

• Sachkova MY, Nordmann EL, Soto Angel JJ, Meeda Y, Górski B, Naumann B, Dondorp D, Chatzigeorgiou M, Kittelmann M, Burkhardt P (2021) Neuropeptide repertoire and 3D anatomy of the ctenophore nervous system. Current Biology 31, 5274–5285. (preprint avialable here bioRxiv).

• Burkhardt P and Jékely G (2021) Evolution of Synapses and Neurotransmitter Systems: The Divide-and-Conquer Model for Early Neural Cell-Type Evolution. Current Opinion in Neurobiology (71) 127-138. (preprint available here Preprints).

• Musser JM, Schippers KJ, Nickel M, Mizzon G, Kohn AB , Pape C, Hammel JU, Wolf F, Liang C, Hernández-Plaza A, Achim K, Schieber NL, Francis WR, Vargas S, Kling S, Renkert M, Feuda R, Gaspar I, Burkhardt P, Bork P, Beck M, Kreshuk A, Wörheide G, Huerta-Cepas J, Schwab Y, Moroz LL, Arendt D (2021) Profiling cellular diversity in sponges informs animal cell type and nervous system evolution. Science 374 (6568), 717-723. (preprint avialable here bioRxiv).

• Hake KH, West PT, McDonald K, Laundon D, Feng C, Burkhardt P, Richter D, Banfield JF, King N (2021) Colonial choanoflagellate isolated from Mono Lake harbors a microbiome. bioRxiv 437421.

• Goehde RA*, Naumann B*, Laundon D, Imig C, McDonald K, Cooper BH, Varoqueaux F, Fasshauer D, Burkhardt P (2021) Choanoflagellates and the ancestry of neurosecretory vesicles. Phil. Trans. R. Soc. B 376: 20190759. (*joint 1^st author). (preprint avialable here bioRxiv).

• Nauman B, Burkhardt P (2019) Spatial cell disparity in the colonial choanoflagellate Salpingoeca rosetta. Frontiers in Cell and Developmental Biology 7 (231). (preprint avialable here bioRxiv).

• Sachkova M, Burkhardt P (2019) Exciting times to study the identity and evolution of cell types. Development 146: dev178996.

• Laundon D, Larson B, McDonald K, King N, Burkhardt P (2019) The architecture of cell differentiation in choanoflagellates and sponge choanocytes. PLoS Biology 17 (4): e3000226. (recommended by F1000) (preprint avialable here bioRxiv).

• Kollmar M, Welz T, Straub F, Alzahofi N, Hatje K, Briggs DA, Samol-Wolf A, Burkhardt P, Hume A, Kerkhoff E (2019) Animal evolution coincides with a novel degree of freedom in exocytic transport processes. bioRxiv 452185.

• Morey C, Kienle CN, Klöpper TH, Burkhardt P, Fasshauer D (2017) Evidence for a conserved inhibitory binding mode between the membrane fusion assembly factors Munc18 and syntaxin in animals. Journal of Biological Chemistry 292 (50): 20449-20460.

• Burkhardt P, Sprecher SG (2017) Evolutionary origin of synapses and neurons – Bridging the gap. BioEssays 39 (10): 1700024.

• Hoffmeyer TT and Burkhardt P (2016) Choanoflagellate models – Monosiga brevicollis and Salpingoeca rosetta. Current Opinion in Genetics and Development (39) 42-47.

• Bhattacharyya M*, Stratton MM*, Going CC*, McSpadden E, Huang Y, Susa AC, Elleman A, Cao YM, Pappireddi N, Burkhardt P, Gee C, Barros T, Schulman H, Williams ER, Kuriyan J (2016) Molecular mechanism of activation-triggered subunit exchange in Ca²⁺/calmodulin-dependent protein kinase II. Elife 5: e13405. (*joint 1^stauthor).

• Burkhardt P (2015) The origin and evolution of synaptic proteins – choanoflagellates lead the way. Journal of Experimental Biology (218): 506-514.

• Burkhardt P, Gronborg M, McDonald K, Sulur T, Wang Q, King N (2014) Evolutionary insights into premetazoan functions of the neuronal protein Homer. Molecular Biology and Evolution 31 (9): 2342–2355.

• Demircioglu FD, Burkhardt P, Fasshauer D (2014) The SM protein Sly1 accelerates assembly of the ER-Golgi SNARE complex. Proceedings of the National Academy of Sciences 111 (38): 13828-13833.

• Sebe-Pedros A*, Burkhardt P*, Sánchez-Pons N, Fairclough SR, Lang F, King N, Ruiz- Trillo I (2013) Insights into the origin of metazoan filopodia and microvilli. Molecular Biology and Evolution 30 (9): 2013-2023 (*joint 1^st author).

• Colbert KN, Hattendorf DA, Weiss TM, Burkhardt P, Fasshauer D, Weis WI (2013) Syntaxin1a variants lacking an N-peptide or bearing the LE mutation bind to Munc18a in a closed conformation. Proceedings of the National Academy of Sciences, 110 (31): 12637-42.

• Meijer M*, Burkhardt P*, de Wit H, Toonen RF, Fasshauer D, Verhage M (2012) Munc18-1 mutations that strongly impair SNARE-complex binding support normal synaptic transmission. EMBO Journal 31 (9): 2156-2168 (*joint 1^st author). (recommended by F1000)

• Burkhardt P, Stegmann CM, Cooper B, Kloepper TH, Imig C, Varoqueaux F, Wahl MC, Fasshauer D (2011) Primordial neurosecretory apparatus identified in the choanoflagellate Monosiga brevicollis. Proceedings of the National Academy of Sciences, 108 (37): 15264-15269.

• Burkhardt P, Hattendorf DA, Weis WI, Fasshauer D (2008) Munc18 controls SNARE assembly through its interaction with the syntaxin N-peptide. EMBO Journal 27 (7): 923-933.(recommended by F1000)