Reflections On Contributing To “Big Discoveries” About The Fly Clock: Our Fortunate Paths As Post-Docs With 2017 Nobel Laureates Jeff Hall, Michael Rosbash, And Mike Young

In the early 1980s Jeff Hall and Michael Rosbash at Brandeis University and Mike Young at Rockefeller University set out to isolate the period (per) gene, which was recovered in a revolutionary genetic screen by Ron Konopka and Seymour Benzer for mutants that altered circadian behavioral rhythms. Over the next 15 years the Hall, Rosbash and Young labs made a series of groundbreaking discoveries that defined the molecular timekeeping mechanism and formed the basis for them being awarded the 2017 Nobel Prize in Physiology or Medicine. Here the authors recount their experiences as post-docs in the Hall, Rosbash and Young labs from the mid-1980s to the mid-1990s, and provide a perspective of how basic research conducted on a simple model system during that era profoundly influenced the direction of the clocks field and established novel approaches that are now standard operating procedure for studying complex behavior

Fruitless, Doublesex And The Genetics Of Social Behavior In Drosophila Melanogaster

Two genes coding for transcription factors, fruitless and doublesex, have been suggested to play important roles in the regulation of sexually dimorphic patterns of social behavior in Drosophila melanogaster. The generalization that fruitless specified the development of the nervous system and doublesex specified non-neural tissues culminated with claims that fruitless was both necessary and sufficient to establish sex-specific patterns of behavior. Several recent articles refute this notion, however, demonstrating that at a minimum, both fruitless and doublesex are involved in establishing sexually dimorphic features of neural circuitry and behavior in fruit flies

Circadian Fluctuations Of Period Protein Immunoreactivity In The CNS And Visual System Of Drosophila

When the protein encoded by the period (per) gene, which influences circadian rhythms in Drosophila melanogaster, was labeled with an anti- per antibody in adult flies sectioned at different times of day, regular fluctuations in the intensity of immunoreactivity were observed in cells of the visual system and central brain. These fluctuations persisted in constant darkness. Time courses of the changing levels of staining were altered in the per-short mutant: in light/dark cycles, the phase was earlier than in wild-type, and in constant darkness the period was shorter. In a per-long mutant and in behaviorally subnormal germline transformants (involving transduced per DNA), staining intensities were much fainter than in wild-type. Factors involved in initiating or maintaining the per protein cycling were investigated by examining the immunoreactivity in visual system mutants and by exposing wild-type flies to altered light/dark regimes. These genetic and environmental manipulations affected the expression of the per protein in ways that usually parallelled their effects on circadian behaviors

Active Learning Outside The Classroom: Implementation And Outcomes Of Peer-Led Team-Learning Workshops In Introductory Biology

Study group meetings (SGMs) are voluntary-attendance peer-led team-learning workshops that supplement introductory biology lectures at a selective liberal arts college. While supporting all students’ engagement with lecture material, specific aims are to improve the success of underrepresented minority (URM) students and those with weaker backgrounds in biology. Peer leaders with experience in biology courses and training in science pedagogy facilitate work on faculty-generated challenge problems. During the eight semesters assessed in this study, URM students and those with less preparation attended SGMs with equal or greater frequency than their counterparts. Most agreed that SGMs enhanced their comprehension of biology and ability to articulate solutions. The historical grade gap between URM and non-URM students narrowed slightly in Biology 2, but not in other biology and science, technology, engineering, and mathematics courses. Nonetheless, URM students taking introductory biology after program implementation have graduated with biology majors or minors at the same rates as non-URM students, and have enrolled in postcollege degree programs at equal or greater rates. These results suggest that improved performance as measured by science grade point average may not be necessary to improve the persistence of students from underrepresented groups as life sciences majors

A Drosophila DEG/ENaC Subunit Functions Specifically In Gustatory Neurons Required For Male Courtship Behavior

Detection of specific female pheromones stimulates courtship behavior in Drosophila melanogaster males, but the chemosensory molecules, cells, and mechanisms involved remain poorly understood. Here we show that ppk25, a DEG/ENaC ion channel subunit required for normal male response to females, is expressed at highest levels in a single sexually dimorphic gustatory neuron of most taste hairs on legs and wings, but not in neurons that detect courtship-inhibiting pheromones or food. Synaptic inactivation of ppk25-expressing neurons, or knockdown of ppk25 expression in all gustatory neurons, significantly impairs male response to females, whereas gustatory expression of ppk25 rescues the courtship behavior of ppk25 mutant males. Remarkably, the only other detectable albeit significantly weaker expression of ppk25 occurs in olfactory neurons implicated in modulation of courtship behavior. However, expression of ppk25 in olfactory neurons is not required for male courtship under our experimental conditions. These data show that ppk25 functions specifically in peripheral taste neurons involved in activation of courtship behavior, an unexpected function for this type of channel. Furthermore, our work identifies a small subset of gustatory neurons with an essential role in activation of male courtship behavior, most likely in response to female pheromones

The Role Of Cuticular Pheromones In Courtship Conditioning Of Drosophila Males

Courtship conditioning is an associative learning paradigm in Drosophila melanogaster, wherein male courtship behavior is modified by experience with unreceptive, previously mated females. While the training experience with mated females involves multiple sensory and behavioral interactions, we hypothesized that female cuticular hydrocarbons function as a specific chemosensory conditioned stimulus in this learning paradigm. The effects of training with mated females were determined in courtship tests with either wild-type virgin females as courtship targets, or with target flies of different genotypes that express distinct Cuticular hydrocarbon (CH) profiles. Results of tests with female targets that lacked the normal CH profile, and with male targets that expressed typically female CH profiles, indicated that components of this CH profile are both necessary and sufficient cues to elicit the effects of conditioning. Results with additional targets indicated that the female-specific 7,11-dienes, which induce naive males to court, are not essential components of the conditioned Stimulus. Rather, the learned response was significantly correlated with the levels of 9-pentacosene (9-P), a compound found in both males and females of many Drosophila strains and species. Adding 9-P to target flies showed that it stimulates courting males to attempt to copulate, and confirmed its role as a component of the conditioned stimulus by demonstrating dose-dependent increases in the expression of the learned response. Thus, 9-P can contribute significantly to the conditioned Suppression of male courtship toward targets that express this pheromone

Principles And Practices Fostering Inclusive Excellence: Lessons From The Howard Hughes Medical Institute’s Capstone Institutions

Best-practices pedagogy in science, technology, engineering, and mathematics (STEM) aims for inclusive excellence that fosters student persistence. This paper describes principles of inclusivity across 11 primarily undergraduate institutions designated as Capstone Awardees in Howard Hughes Medical Institute’s (HHMI) 2012 competition. The Capstones represent a range of institutional missions, student profiles, and geographical locations. Each successfully directed activities toward persistence of STEM students, especially those from traditionally underrepresented groups, through a set of common elements: mentoring programs to build community; research experiences to strengthen scientific skill/identity; attention to quantitative skills; and outreach/bridge programs to broaden the student pool. This paper grounds these program elements in learning theory, emphasizing their essential principles with examples of how they were implemented within institutional contexts. We also describe common assessment approaches that in many cases informed programming and created traction for stakeholder buy-in. The lessons learned from our shared experiences in pursuit of inclusive excellence, including the resources housed on our companion website, can inform others’ efforts to increase access to and persistence in STEM in higher education

Pharmacological And Genetic Reversal Of Age-Dependent Cognitive Deficits Attributable To Decreased Presenilin Function

Alzheimer\u27s disease (AD) is the leading cause of cognitive loss and neurodegeneration in the developed world. Although its genetic and environmental causes are not generally known, familial forms of the disease (FAD) are attributable to mutations in a single copy of the Presenilin (PS) and amyloid precursor protein genes. The dominant inheritance pattern of FAD indicates that it may be attributable to gain or change of function mutations. Studies of FAD-linked forms of presenilin (psn) in model organisms, however, indicate that they are loss of function, leading to the possibility that a reduction in PS activity might contribute to FAD and that proper psn levels are important for maintaining normal cognition throughout life. To explore this issue further, we have tested the effect of reducing psn activity during aging in Drosophila melanogaster males. We have found that flies in which the dosage of psn function is reduced by 50% display age-onset impairments in learning and memory. Treatment with metabotropic glutamate receptor (mGluR) antagonists or lithium during the aging process prevented the onset of these deficits, and treatment of aged flies reversed the age-dependent deficits. Genetic reduction of Drosophila metabotropic glutamate receptor (DmGluRA), the inositol trisphosphate receptor (InsP(3)R), or inositol polyphosphate 1-phosphatase also prevented these age-onset cognitive deficits. These findings suggest that reduced psn activity may contribute to the age-onset cognitive loss observed with FAD. They also indicate that enhanced mGluR signaling and calcium release regulated by InsP(3)R as underlying causes of the age-dependent cognitive phenotypes observed when psn activity is reduced