Jia, Kailiang

Animals rely on the integration of a variety of external cues to understand and respond appropriately to their environment. The relative amounts of food and constitutively secreted pheromone detected by the nematode C. elegans determines how it will develop and grow. Starvation conditions cause the animal to enter a protective stage, termed dauer. Dauer animals are non-eating, long-lived and stress resistant. Yet, when these animals are introduced to food replete conditions they will recover from dauer and proceed into normal development. Furthermore, food restriction has been demonstrated to extend the lifespan of a wide-range of species including C. elegans. However, the exact mechanism by which food signals are detected and transduced by C. elegans to influence development and longevity remains unknown. Here, we identify a G protein-coupled receptor (GPCR) DCAR-1 that acts in two chemosensory neurons to mediate food signaling in an autophagy-related manner. The DCAR-1 ligand Dihydrocaffeic acid (DHCA) competes with dauer-inducing pheromone to promote growth. DHCA is a key intermediate in the shikimate pathway, which is required to synthesize folate and aromatic amino acids. We report that dcar-1 mutations influence dauer formation and extend wildtype lifespan via a mechanism of dietary restriction. Moreover, we show that the lifespan extension of dcar-1 mutants is completely dependent on autophagy gene atg- 18. Furthermore, our data suggests metabolites derived from shikimate are food signals that control aging and dauer development through GPCR signaling in C. elegans. These studies will contribute to the delineation of mechanisms behind the beneficial effects of dietary restriction in eukaryotic organisms.

The conserved insulin growth factor IGF signaling pathway is one of the major regulators of lifespan in
many species including C. elegans. In C. elegans the insulin/IGF-like receptor is encoded by the daf-2
gene, mutations in which result in lifespan extension. The daf-2 activity in the nervous system controls
these phenotypes cell nonautonomously. Interestingly, the longevity phenotype of daf-2 mutant worms
is dependent on macroautophagy hereafter autophagy. Autophagy is a highly conserved lysosomal
degradation pathway involved in the removal of long-lived proteins and cytoplasmic organelles. During
autophagy, cellular components are sequestered into the double-membrane autophagosomes and
delivered to lysosomes for degradation. Increasing evidence has emerged that the autophagy process
is a central regulator of lifespan that is required for the effects of DAF-2 signaling, dietary restriction and
some mitochondrial mutations on C. elegans longevity. It is unknown however whether autophagy
activity in every tissue or in a single tissue mediates the influence of these longevity signals. To
address this question, we examined the tissue requirement of the autophagy gene atg-18 for the
lifespan of wild type animals and the daf-2 mutant. We discovered that neurons and intestinal cells are
two key tissues where atg-18 mediates the effect of DAF-2 insulin-like signaling on lifespan, suggesting
autophagy acts cell nonautonomously in controlling C. elegans adult longevity. Moreover, we found that
neuronal release of neuropeptides is required for the cell non-autonomous function of neuronal
autophagy activity in controlling C. elegans lifespan.

Purpose: This study was designed to define the antibiotic resistance index of the
cultivable oral microbiome to Amoxiacilin Clavulanic acid, Vancomycin, Ciprofloxacin,
Clarithomycin, Chlorotetracyclin, Bacitracin, Kanamycin and Tobramycin using a new method
adapted from the Kirby Bauer assay.
Method: Oral wash samples were collected from 2 current smokers and 2 nonsmokers. Bacterial
community were pelleted by centrifugation and used to create a lawn for the assay employing
standard disk diffusion assay. Zones of inhibition and number of colonies in the zone were
recorded. Mean values of inhibition zones were compared to established databases to draw
conclusions.
Result: The zones of inhibition of Bacitracin antibiotics shows that several bacteria from one of
the non smokers were resistant to Bacitracin, while the smokers showed marked susceptibility.
Conclusion: The new method developed in our lab yielded consistent set of data which serve as
criteria for determining resistance of the oral microbiome to antibiotics. Quite remarkably, it is
known that pathogenic beta Streptococci are susceptible to Bacitracin while non-pathogens are
not; confirming that healthy persons harbor the healthy strains of streptococci. However the
unanswered question is …. Could these normal biota pick up genes and become resistant too?
Only time and human habits will decide but we have developed a baseline and an easy method
for testing.

FAU's Office of Undergraduate Research and Inquiry hosts an annual symposium where students engaged in undergraduate research may present their findings either through a poster presentation or an oral presentation.

Caenorhabditis elegans optionally enter into a dauer diapause phase that results
in a prolonged life in a semi-dormant state. Entry into and recovery from dauer diapause
includes many physical changes in body structure, physiology, and gene expression.
Entry into dauer diapause is regulated by several signaling pathways including
transforming growth factor (TGF-β). Autophagy plays an important role in dauer
formation and recover. During dauer transformation autophagy is up-regulated and may
play a role in remodeling the molecular structure for long term survival during dauer
diapause. This research helps determine the role of autophagy in dauer development and
recovery mediated through the TGF-β signaling pathway. This research also determines
in which tissue autophagy is necessary for dauer formation and recovery through TGF-β signaling. This research is shedding light on the function of autophagy in the TGF-β
signaling pathway, both processes of which have been linked to tumorigenesis, heart
disease and cancer.

In the round worm C. elegans, it has recently been shown that autophagy, a highly
conserved lysosomal degradation pathway that is present in all eukaryotic cells, is
required for maintaining healthspan and for increasing the adult lifespan of worms fed
under dietary restriction conditions or with reduced IGF signaling. It is currently
unknown how extracellular signals regulate autophagy activity within different tissues
during these processes and whether autophagy functions cell-autonomously or nonautonomously.
We have data that for the first time shows autophagy activity in the
neurons and intestinal cells plays a major role in regulating adult lifespan and the
longevity conferred by altered IGF signaling and dietary restriction, suggesting
autophagy can control these phenotypes cell non-autonomously. We hypothesize that
autophagy in the neurons and intestinal cells is an essential cellular process regulated by
different signaling pathways to control wild type adult lifespan, IGF mediated longevity and dietary restriction induced longevity. Excitingly we also have found that in animals
with reduced IGF signaling autophagy can control longevity in only a small subset of
neurons alone. Autophagy in either specific individual chemosensory neurons or a small
group of them is completely sufficient to control IGF mediated longevity. This work
provides novel insight to the function and regulation of autophagy which will help shed
light on understanding this essential process in higher organisms, including mammals.

We recently discovered that autophagy, a conserved lysosomal degradation pathway, is necessary for increased lifespan and dauer morphogenesis of daf-2 mutant Caenorhabditis elegans. daf-2 encodes the worm orthologue of an insulin-like growth factor receptor. Moreover, we found neuronal autophagy activity is sufficient to fulfill this requirement. In this study we used the unc-42 promoter to express autophagy gene atg-18 in a subset of C. elegans neurons to examine whether autophagy activity in these neurons is sufficient to execute its function in extension of lifespan and completion of dauer morphogenesis in daf-2 mutants. Here we show expression of atg-18 in these ons fails to rescue the effect of atg-18 mutations on the longevity and dauer morphogenesis of daf-2 mutant worms, indicating that the requirement of neuronal autophagy in C. elegans for these effects is specific to neurons where unc-42 promoter is not active.

The probability of humans developing neurodegenerative diseases increases as one ages. So the purpose of this study is to use the nematode Caenorhabditis elegans as a genetic model for determining if they develop age-dependent neuronal changes.

The conserved insulin growth factor IGF signaling pathway is one of the major regulators of lifespan in many species including C. elegans. In C. elegans the insulin/IGF-like receptor is encoded by the daf-2 gene, mutations in which result in lifespan extension, fat accumulation and dauer formation. The daf-2 activity in the nervous system controls these phenotypes cell non-autonomously. Interestingly, the longevity phenotype of daf-2 mutant worms is dependent on macroautophagy hereafter autophagy. Autophagy is a highly conserved lysosomal degradation pathway involved in the removal of long-lived proteins and cytoplasmic organelles. During autophagy, cellular components are sequestered into the double-membrane autophagosomes and delivered to lysosomes for degradation. Increasing evidence has emerged that the autophagy process is a central regulator of lifespan that is required for the effects of DAF-2 signaling, dietary restriction and some mitochondrial mutations on C. elegans longevity. It is unknown however whether autophagy activity in every tissue or in a single tissue mediates the influence of these longevity signals. To address this question, we examined the tissue requirement of autophagy gene atg-18 for the lifespan of wild type animals and the daf-2 mutant. We discovered that neurons and intestinal cells are two key tissues where atg-18 mediates the effect of DAF-2 insulin-like signaling on lifespan, fat accumulation and dauer morphogenesis, suggesting autophagy acts cell non-autonomously in controlling C. elegans dauer formation, fat metabolism and adult longevity.

Autophagy is a lysosomal degradation pathway present in eukaryotes that allows
a cell to break down cytoplasmic proteins and organelles to maintain homeostasis. The
autophagy pathway has been shown to play a significant role in the immune systems
protective response against various bacterial pathogen infections, such as the intestinal
pathogen Salmonella typhimurium, in Caenorhabditis elegans and in mammals. This
study investigated if the autophagy pathway acts in a tissue-specific manner to protect
against S. typhimurium infection in C. elegans. Wild type C. elegans and worms where
the autophagy gene bec-1 was inhibited in different tissues by RNAi treatment were
infected by S. typhimurium and their survival measured. My data showed that the
autophagy gene bec-1 only protected C. elegans against S. typhimurium infection in the
intestinal tissues, suggesting that the autophagy pathway acts in a tissue specific manner
to help protect against Salmonella invasions in C. elegans.