Area: Molecular & Human Genetics
Dr. Bellen received the award most recently due to his transformative observations linking metabolic alterations in mitochondrial function to a host of neurodegenerative diseases. He uses Drosophila as a model system to explore the functions of the nervous system. In so doing, he has developed state of the art technologies to empower the drosophila genetics community. At the same time, he has made seminal observations in neurodevelopment mechanisms including synaptic transmission and Notch signaling. Importantly, he has performed genetic screens in drosophila that have now empowered translational research in combination with human genetic gene discovery.
Dr. Bellen's nomination was based on the following publications:
Yamamoto S, Jaiswal M, Charng WL, Gambin T, Karaca E, Mirzaa G, Wiszniewski W, Sandoval H, Haelterman NA, Xiong B, Zhang K, Bayat V, David G, Li T, Chen K, Gala U, Harel T, Pehlivan D, Penney S, Vissers LE, de Ligt J, Jhangiani SN, Xie Y, Tsang SH, Parman Y, Sivaci M, Battaloglu E, Muzny D, Wan YW, Liu Z, Lin-Moore AT, Clark RD, Curry CJ, Link N, Schulze KL, Boerwinkle E, Dobyns WB, Allikmets R, Gibbs RA, Chen R, Lupski JR, Wangler MF, Bellen HJ. A drosophila genetic resource of mutants to study mechanisms underlying human genetic diseases. Cell. 2014 Sep 25;159(1):200-14. doi: 10.1016/j.cell.2014.09.002.
Nagarkar-Jaiswal S, Lee PT, Campbell ME, Chen K, Anguiano-Zarate S, Gutierrez MC, Busby T, Lin WW, He Y, Schulze KL, Booth BW, Evans-Holm M, Venken KJ, Levis RW, Spradling AC, Hoskins RA, Bellen HJ. A library of MiMICs allows tagging of genes and reversible, spatial and temporal knockdown of proteins in Drosophila. Elife. 2015 Mar 31;4. doi: 10.7554/eLife.05338.
Liu L, Zhang K, Sandoval H, Yamamoto S, Jaiswal M, Sanz E, Li Z, Hui J, Graham BH, Quintana A, Bellen HJ. Glial lipid droplets and ROS induced by mitochondrial defects promote neurodegeneration. Cell. 2015 Jan 15;160(1-2):177-90. doi: 10.1016/j.cell.2014.12.019. PubMed PMID: 25594180; PubMed Central PMCID: PMC4377295.
Molecular mechanisms of neurotransmitter release: a genetic dissection
Dr. Bellen was recognized for the identification and genetic dissection of the molecular events responsible for the release of neurotransmitter from the nerve terminal and demonstration that synaptotagmin acts as a calcium detector in this process.
Dr. Bellen’s nomination was based on the following publications:
Littleton JT, Stern M, Schulze K, Perin M, Bellen HJ. Mutational analysis of Drosophila synaptotagmin demonstrates its essential role in Ca(2+)-activated neurotransmitter release. Cell. 1993 Sep 24;74(6):947-50.
Schulze KL, Littleton JT, Salzberg A, Halachmi N, Stern M, Lev Z, Bellen HJ. rop, a Drosophila homolog of yeast Sec1 and vertebrate n-Sec1/Munc-18 proteins, is a negative regulator of neurotransmitter release in vivo. Neuron. 1994 Nov;13(5):1099-108.
Littleton JT, Stern M, Perin M, Bellen HJ. Calcium dependence of neurotransmitter release and rate of spontaneous vesicle fusions are altered in Drosophila synaptotagmin mutants. Proc Natl Acad Sci U S A. 1994 Nov 8;91(23):10888-92.
Schulze KL, Broadie K, Perin MS, Bellen HJ. Genetic and electrophysiological studies of Drosophila syntaxin-1A demonstrate its role in nonneuronal secretion and neurotransmission.Cell. 1995 Jan 27;80(2):311-20.