Neurodegeneration Dr. Bellen's current research focuses on an effort to decipher the mechanisms by which mutations in specific genes cause
neurodegeneration, and to this end, he and his colleagues performed unbiased
forward genetic screens in fruitflies that detect the progressive decline in function and morphology of photoreceptor neurons. To date over 165 genes that cause a neurodegenerative phenotype when mutated have been uncovered by Dr. Bellen's group using this strategy. Many of these genes encode homologues of human genes that are known to cause neurodegenerative diseases, including
amyotrophic lateral sclerosis (ALS) (Lou Gehrig's disease),
Charcot-Marie-Tooth (CMT),
Parkinson's disease (PD),
Alzheimer's disease (AD),
Leigh syndrome, and others, and these studies will help provide a much better understanding of the molecular mechanisms by which neurodegeneration occurs. A prevailing theme among these mutants seems to be dysfunction of the neuronal
mitochondria and an increasing inability to deal with
oxidative stress, which manifests as
lipid droplets.
Technology Bellen has pioneered the development of novel technologies that accelerate Drosophila research and are currently used by the majority of fly labs today. Bellen was a leader in the development of
P element-mediated enhancer detection which allows for discovery and manipulation of genes and was the impetus for a collaborative and ongoing project to generate an insertion collection for the community. Furthermore, Bellen and colleagues devised a new transformation technology that permits site-specific integration of very large DNA fragments, which led to the generation of a collection of flies carrying molecularly defined duplications for more than 90% of the Drosophila X-chromosome. Hundreds of Drosophila researchers utilize this collection. Most recently his lab created a new
transposable element (MiMIC) that permits even more downstream manipulations via RMCE (
recombinase-mediated cassette exchange), such as protein tagging and knockdown and large scale
homologous recombination. His research constantly evolves with the changing technology to meet the needs of the Drosophila community.
Neurotransmitter release Bellen has made numerous important contributions in the field of
synaptic transmission in Drosophila. Through unbiased forward genetic screens designed to detect perturbations in neuronal function, he has uncovered many genes involved in synaptic transmission and has used
reverse genetics to help to establish their function. His lab was the first to provide
in vivo evidence that
Synaptotagmin 1 functions as the main Calcium sensor in synaptic transmission and that
Syntaxin-1A plays a critical role in synaptic vesicle (SV) fusion
in vivo. His lab showed that Endophilin and
Synaptojanin control uncoating of SVs, that the V0 component of the
v-ATPase affects SV fusion, that synaptic mitochondria control SV dynamics, and in addition discovered a novel calcium channel involved in SV biogenesis. His pioneering work on synaptic vesicle trafficking molecules was later confirmed in the mouse.
Neuronal Development Bellen and colleagues made important contributions to our understanding of Drosophila peripheral nervous system development and the fine-tuning of aspects of
Notch signaling during this process. These discoveries were made by carrying out multiple forward genetic screens using the mutagen,
ethyl methane sulfonate, as well as
P elements. They discovered the protein Senseless that is required for the development of the peripheral nervous system by boosting the action of
proneural proteins and suppressing the action of Enhancer of split proteins. They also discovered the protein Rumi and determined it was required for
O-glycosylation of Notch at many different sites and found that these sites affect the cleavage of Notch at the membrane. Their research also uncovered a critical amino acid of the Notch protein that modulates its binding with Serrate. Finally, they helped elucidate the functions of several other proteins involved in the Notch pathway, including the roles of Wasp/Arp2/3, Sec15, Tempura, and EHBP-1 in Delta processing and signaling. ==Awards and honors==