Where Are They Now?

Marco Gambino (UROP)

Latest Work: Continuing Studies

Undergraduate Research
As an undergraduate researcher, Marco was involved in a study on Parkinson's disease, a common neurodegenerative disorder. The study focused on investigating the effects of a cannabinoid called CP-55940 on the symptoms of Parkinson's. Marco used Drosophila melanogaster as a model organism to mimic human disease and conducted experiments targeting dopamine transporters with tetanus toxin using the Gal4/UAS system.

Marco's research included four test groups. Two groups were treated with the cannabinoid, while the other two groups served as control and did not receive the treatment. By observing the locomotion and rest behaviors of these groups, Marco aimed to determine whether the cannabinoid could provide protection against the symptoms induced by paraquat, a neurotoxin associated with Parkinson's.

This study conducted by Marco contributes to our understanding of the potential therapeutic effects of marijuana in treating Parkinson's disease.
Lara Gardiner (Keystone Kilachand Honors Project)

Latest Work: Napadow Lab at the Spaulding Rehabilitation Center

Lara, as part of their Keystone Kilachand Honors Project, investigated the impact of depleted serotonin levels on the disturbance of circadian rhythms in fruit flies. Specifically, they aimed to determine whether exposure to sunlight could alleviate this disruption.

In their research, Lara focused on understanding how serotonin depletion affected the internal clock of fruit flies and disrupted their natural sleep-wake cycles. By manipulating serotonin levels in the flies, they observed any changes in their circadian rhythms.

Additionally, Lara explored the potential role of sunlight in mitigating the disruption caused by depleted serotonin levels. They exposed the fruit flies to controlled amounts of sunlight and observed whether this exposure had any positive effects on their circadian rhythms.

Lara's Keystone Kilachand Honors Project contributed to our understanding of the relationship between serotonin, circadian rhythms, and the potential therapeutic effects of sunlight exposure in fruit flies.
Otto Holbrook (UROP, 2022 Francis Bacon Award for Writing in the Natural Sciences)

Latest Work: Ph.D. Student in Medicinal Chemistry & Drug Discovery, Northeastern University

Undergraduate Research

Otto's research focused on understanding Alcohol Use Disorder (AUD) and its underlying mechanisms. He investigated the role of reward memory in driving alcohol-seeking behavior. Specifically, Otto studied the protein Scabrous (SCA) and its involvement in the formation of alcohol reward memories. In previous studies, SCA was implicated in the Notch signaling pathway in Drosophila and shown to play a crucial role in the formation of alcohol reward memories.

To further his understanding, he examined a specific mutant form of SCA called SCA5-120, which was found to inhibit the formation of alcohol reward memories. By comparing the expression rate and localization of endogenous SCA and the SCA5-120 mutant, Otto aimed to uncover the differences between these proteins and their impact on alcohol-related behaviors.

Additionally, he investigated how excessive ethanol exposure affected the expression rate of both endogenous SCA and the SCA5-120 mutant. This provided insights into the changes that occurred in the brain after prolonged alcohol exposure and helped us understand the molecular mechanisms underlying the development and persistence of AUD.

Through his research, Otto hoped to contribute to the understanding of AUD and potentially identify targets for therapeutic interventions that could help individuals struggling with this disorder.
Sehjin Jo

Latest Work: Dr. Jen Wei Liu Lab in the Department of Biology at Boston University

In this research project, Sehjin's objective was to investigate the Circadian Rhythm Circuit in Drosophila Melanogaster. Sehjin focused on mapping and characterizing its anatomy. To achieve this, the GAL-4/UAS system was employed to stain the fruit fly brain and identify the circuit. Additionally, behavioral data was collected using the DAM to analyze the activity patterns of the flies.

The data collected included information from wild type flies, as well as two genetically modified lines: Bloomington stock 39839 targeting 5-HT2B neurons and tagged with GFP, and a cross between Bloomington stock 41275 targeting DNIP neurons and UAS 8515 for EGFP. To confirm the success of the staining process and observe the resulting brain images, fluorescence microscopy was utilized.

Sehjin's ultimate goal in this research was to gain a deeper understanding of the Circadian Rhythm Circuit in Drosophila Melanogaster and its role in anticipating and adapting to environmental changes.
Derek Kolodziejski (UROP)

Latest Work: Chemistry Department at Blueprint Medicines in Cambridge, MA

Derek employed the DREADD (Designer Receptors Exclusively Activated by Designer Drugs) method to investigate the roles of D1 and D2 dopamine receptors in alcohol addiction using the model organism, Drosophila melanogaster. The bipartite GAL4/UAS system, combined with CNO-gated DREADDs, allowed for the selective modulation of these receptors. By manipulating the activity of D1 and D2 receptors in response to designer drugs, Derek aimed to elucidate their potential involvement in the reward pathway and enhance our understanding of addiction.

Throughout the addiction paradigm, which includes dependence, abstinence, and binge phases, Derek measured the effects of up and down-regulating both D1 and D2 receptors on acute alcohol tolerance. This was achieved by quantifying the binge consumption of ethanol-infused food. By selectively activating or inhibiting these receptors in specific neuronal populations, Derek aimed to uncover the impact of D1 and D2 receptor modulation on the addictive behavior of the flies.

This study using the DREADD method provided valuable insights into the potential roles of D1 and D2 receptors in alcohol addiction. By combining the power of DREADDs with the Drosophila model organism, Derek was able to explore the neurobiological mechanisms underlying addiction and contribute to our overall understanding of this complex disorder.
Samuel Krick (UROP)

Latest Work: Continuing Studies at Boston University

In his study on the comorbidity of depression and alcoholism, Samuel utilized a powerful genetic tool called the GAL4/UAS system to specifically manipulate the activity of the Shibire protein in Drosophila melanogaster.

The GAL4/UAS system is a widely employed method in Drosophila research that allows for precise targeting of gene expression in specific tissues or cell types. It involves two components: the GAL4 driver and the UAS responder.

In this case, Samuel used the 5-HT-Gal4 driver line, which expresses the GAL4 protein specifically in serotonergic neurons. Serotonin, also known as 5-hydroxytryptamine (5-HT), is a neurotransmitter implicated in mood regulation. By using this specific driver, Samuel was able to selectively control the expression of the Shibire protein in the serotonergic neurons of the flies.

On the other hand, the UAS-Shibire responder line contained a modified form of the Shibire gene that was tagged with a UAS (Upstream Activating Sequence). The UAS sequence acts as a binding site for the GAL4 protein, enabling the activation or repression of gene expression in the presence of GAL4.

By crossing the 5-HT-Gal4 driver line with the UAS-Shibire responder line, Samuel generated flies in which the expression of Shibire could be manipulated specifically in serotonergic neurons. This allowed him to induce depression-like behaviors by inactivating Shibire in these specific neurons, leading to disruptions in synaptic vesicle endocytosis and decreased release of serotonin.

The GAL4/UAS system provided Samuel with a powerful tool to investigate the role of Shibire in depression-related behaviors, offering a precise and targeted approach to studying the complex relationship between serotonin, depression, and alcoholism in Drosophila.
Mattie Love (UROP)

Latest Work: Continuing Studies

Undergraduate Research
In their studies, Mattie assessed the effectiveness of using Drosophila Activity Monitors (DAMs) in a two-choice preference assay with fruit flies. The aim was to gather quantitative data on fly behavior and preferences using DAMs, which track fly movement through infrared beams.

To examine the flies' preference for food, Mattie deprived them of food and offered them a choice between food and an empty option. The DAMs successfully collected time-stamped position readings, revealing that the flies initially preferred the side of the tube with food. Over time, their preferences oscillated, aligning with patterns observed in the movement graphs, indicating periods of activity and rest.

Furthermore, Mattie collected preliminary data using flies dependent on ethanol. These flies were given a choice between ethanol and non-ethanol containing food. Although a larger sample size is necessary for definitive results, the DAMs exhibited potential in quantitatively measuring ethanol preference based on position and movement. This suggests that DAMs could serve as an alternative to current assays relying on odor and consumption levels.

Overall, this study demonstrates the viability of using DAMs to gather behavioral data from fruit flies in a two-choice preference assay. Further research with larger sample sizes could provide valuable insights into fly behavior and preferences.
Eddie Miller (UROP)

Latest Work: Clinical Research Study Assistant in the Laboratory of Scott Marek at University of Washington School of Medicine – St. Louis, MO

Undergraduate Research
Eddie's project focused on investigating how the manipulation of the gut microbiome could influence the brain's usage of serotonin. Through the utilization of the GAL4/UAS system, Eddie aimed to express toxins and fluorescent proteins in specific serotonin receptors. This approach enabled the manipulation of receptor function and visualization of their concentration in the brains of fruit flies.

By administering antibiotics to these flies, Eddie intended to gain a comprehensive understanding of how disruptions in the gut microbiome could lead to significant changes in key aspects of the brain via the gut-brain axis. The project aimed to shed light on the intricate relationship between the gut microbiome and serotonin utilization in the brain, employing genetic manipulation techniques and exploring the effects of microbiome disturbances on brain function.
Brandon Molligoda (UROP Supplies Award, 2022 Francis Bacon Award for Writing in the Natural Sciences)

Latest Work: M.D. Student, University of Central Florida

Undergraduate Research
Brandon conducted a research project that focused on investigating the protein called scabrous. This protein had been previously linked to the formation of alcohol-induced reward memories in Drosophila melanogaster. The main goal of Brandon's project was to understand how alcohol paired vapor conditioning affected the expression of wild type and mutant strains of scabrous in fruit flies.

In addition to this project, Brandon also worked on a review paper that examined the behavioral implications of the downstream products of ethanol metabolism in relation to alcohol use disorder (AUD). The paper aimed to synthesize existing literature and proposed a new conceptual model of AUD that took into consideration the demonstrated effects of these metabolites.
Shreya Nandyala (Independent Study)

Latest Work: Student at University of California – Berkeley

CTY Research
Shreya, a student researcher, conducted a literature review on the effects of music therapy and meditation on cognitive decline. The review found evidence supporting the use of both meditation and passive music therapy in reducing stress, improving quality of life, and enhancing sleep in various populations.
LJ Ullman (UROP Supplies Award)

Latest Work: Research Assistant in Nephrology, Yale School of Medicine

Undergraduate Research
LJ investigated the role of a gene called scabrous (SCA) in the formation of long-term memory related to alcohol reward in Drosophila melanogaster. LJ conducted research on how mutant variants of the SCA gene affected conditioned behavior and explored the differential anatomical expression of SCA in the Drosophila brain. By studying these aspects, LJ aimed to gain insights into the role of the SCA gene in memory formation and its potential implications in alcohol-related behaviors.
Joshua Rong (UROP)

Latest Work: Continuing Studies

Josh conducted a research project aimed at understanding the mechanisms of learning and memory in Drosophila melanogaster. Using the GAL4/UAS system, specific fly strains were bred to investigate the significance of dopamine, serotonin, and norepinephrine in pavlovian learning. The halorhodopsin strain was utilized to individually silence each neurotransmitter and compare their performance to control groups. By analyzing the differences in information recall, Josh aimed to gain insights into the specific roles that these neurotransmitters play in classical conditioning. Additionally, the study also aimed to explore if imbalances in neurotransmitter ratios, which may be observed in certain mental illnesses, have an impact on learning abilities.
Lily Tong (Directed Study)

Latest Work: Research Technician in the Laboratory of Mark Howe, Department of Psychological & Brain Sciences at Boston University

Lily conducted a research project focused on examining the expression of the Dysbindin (Dysb) gene in Drosophila melanogaster. The Dysb gene has been linked to an increased risk of schizophrenia, specifically negative symptoms, in humans. To investigate this further, the study utilized the GAL4/UAS system to genetically manipulate neurons that expressed dysb. The primary objective was to identify the specific neurons with dysb expression and explore the behavioral consequences of manipulating these neurons.
Indu Vaddiparti (Independent Study)

Latest Work: Continuing Studies

Indu conducted a research review paper that examined the insufficient amount of neuroscientific research on sexual orientation within neurodivergent populations, specifically individuals with Down Syndrome and Autism Spectrum Disorder. The study investigated the neuroanatomical and developmental factors that contribute to increased sexual fluidity in individuals with these conditions. It highlighted the limited existing research in this area and the absence of comprehensive educational systems to support these populations in understanding and accepting their sexuality. The main objective of the paper was to raise awareness about diverse sexuality and the healthcare disparities that exist within these neurodivergent communities.
Ziyu (Ivan) Zhao (Independent Study)

Latest Work: Clinical Research Coordinator at Massachusetts General Hospital in the Eating Disorder Clinic and Research Program

Ivan conducted a recent literature review to investigate the interplay between sex hormones, personality traits, and eating disorders. The review aimed to address the knowledge gaps surrounding the potential mediating or moderating role of personality in the relationships between sex hormones and eating pathology, as well as the underlying neural mechanisms involved. Ivan's findings, published in the research summary, revealed that traits such as aggressiveness, impulsivity, and obsessive-compulsiveness could potentially mediate or moderate the connections between sex hormones and eating pathology, primarily among females. Moreover, Ivan proposed a neural mechanism that posited the density of sex hormone receptors in the mesocorticolimbic dopamine pathway as a key factor. To advance future research in this field, Ivan recommended the utilization of comprehensive personality measurements and the examination of temperament's mediation and moderation effects, while also considering hormonal fluctuations across menstrual cycles in women. Additionally, Ivan suggested incorporating techniques such as electroencephalography and functional magnetic resonance imaging to directly assess brain activity and validate the presented findings.
RISE Program
Research in Science & Engineering (RISE) is a program for students passionate about the sciences in their junior year of high school. Students spend six weeks at Boston University conducting laboratory research and advancing their STEM knowledge and skills.

Drosophila Melanogaster projects include:

1. NPF Regulation of Natural Reward
2. dUCH Functioning Underlying Parkinsons Disease-Like Symptoms
3. Role of Corazonin in Stress Response

2023 Cohort

Maggie Zhou

Latest Work: Continuing Studies

RISE Research
Parkinson’s disease (PD) is the second most common neurodegenerative disease characterized by degeneration of dopamine neurons and is often associated with symptoms of motor dysfunction. Additionally, a common non-motor symptom found among PD patients is disruption in their sleep-wake cycles. This study investigated the role of dopamine neurons in the sleep-wake cycles of fruit flies. By using optogenetics to chronically deactivate dopamine neurons, we were able to measure the effect of such deactivation on the sleep and activity patterns of the flies using the Drosophila Activity Monitoring System. We found that chronic inactivation of dopamine neurons caused fruit flies to sleep for longer and exhibit less activity during the light cycle. This suggests that dopamine neurons play a significant role in regulating sleep in fruit flies, and that the inactivation of dopamine neurons in fruit flies is able to model the sleep-wake abnormalities seen in PD. Our findings open up a new area of research into the effects of other PD-related features on sleep-wake cycles, as well as the specific mechanisms underlying the sleep disturbances associated with PD.

2022 Cohort

Julia Banuelos

Latest Work: Student at Dartmouth College

RISE Research
Conducted a study that focused on the role of octopamine neurons in heterospecific aggression. By crossing a GAL-4 line encoding for octopamine with halorhodopsin, upon exposure to yellow light, the neurons were acutely inhibited and the behavioral response was observed in a fly fight chamber.
Ashley Deng

Latest Work: Student at Rice University

RISE Research
Antidepressants are one of the most widely prescribed treatments for depression, with about one-third of those with severe depression using the medication. Thus, antidepressant efficacy is essential to ensure quick and complete remission of depressive symptoms. However, recent research concerning antidepressant efficacy has noted a phenomenon known as the latency period, in which antidepressant treatment often takes 2-3 weeks before becoming effective. During this latency period, suicidal tendencies and depressive symptoms are often heightened, making the understanding of this occurrence crucial to future antidepressant development. It has been suggesed that the activation of the 5-HT1A autoreceptors during antidepressant treatment are the cause of this delayed onset. By sending inhibitory feedback to stop serotonergic neurons from firing when extracellular serotonin levels are raised, autoreceptors are able to combat the effects of antidepressant treatment. It is only when the autoreceptor is eventually desensitized to the raised levels of extracellular serotonin that the latency period ends. This study uses drosophila melanogaster, or fruit flies, as a model to propose a 5-HT1A autoreceptor-based model of the latency period in antidepressant treatment. Utilizing the GAl-4/UAS optogentic system - in which genes coding for light-sensitive proteins are introduced into specific cells to control cell activity using light - a GAL-4 line coding for 5-HT1A autoreceptors was crossed with a UAS line coding for channelrhodopsin. Thus, all 5-HT1A autoreceptors in the F1 generation were able to be acutely activated through red light exposure, allowing the examination of increased expression of 5-HT1A autoreceptors on the latency period of antidepressive treatment.
Layla Manaswini Palutla

Latest Work:
Student at University of Colorado, Denver

RISE Research
Transgenic fruit flies (Drosophila melanogaster) are a suitable model in investigating behavioral variation due to neurodegenerative diseases. Disruption of olfactory reception is a common early symptom of Alzheimer’s disease and Parkinson’s disease. Evidence shows that Drosophila melanogaster additionally loses olfactory sensation prior to vision loss. Choline acetyltransferase (ChAT) is an enzyme which plays a major role in synthesizing the neurotransmitter acetylcholine, which has shown to have strong expression within the central nervous system of Drosophila and is associated with olfactory reception. This model proposes using the GAL4/UAS system, a gene manipulation method in fruit flies to chronically activate ChAT in fruit flies and observing the changes in olfaction. The proposed methodology entails crossing a GAL4 ChAT line and a Transient Receptor Potential (TRP) Channel line. This cross allows for the chronic activation of cholinergic neurons within the flies. Flies are sexed and virgin female Gal4 flies are placed in a vial with a male TRP fly and the resultant progeny can be tested at 28°C. Olfactory aversion to piperine, putrescine and benzaldehyde is measured in behavioral chambers called DAMs (Drosophila Activity Monitors). Aversion is measured by the climbing rate from each odor stimulus in the DAMs. Additionally, fluorescence microscopy is used to analyze regions of the brain that were affected through this cross. Assessing the aversion changes in the model flies can provide insight in the cholinergic connection to olfactory reception in flies and future drug targets for diseases like Parkinson’s and Alzheimer’s.

2021 Cohort

Vedanti Bhargava
Shreya Kaushik
Vedanti Bhargava & Shreya Kaushik

Vedanti's Latest Work: Student at Johns Hopkins University
Shreya's Latest Work: Student at Georgetown University

RISE Research
Current research on short neuropeptide F (sNPF) and neuropeptide F (NPF), the homolog of mammalian neuropeptide Y (NPY), has demonstrated the role of neuropeptides in regulating Drosophila melanogaster behavior. The majority of NPF and sNPF interactions are facilitated by their G-protein coupled receptors, NPFR1 and sNPFR (sNPFR1), which generate a second-messenger cascade. Pathways between NPFR1, sNPFR1, and NPF and sNPF expressing neurons are extended throughout the Drosophila organism, indicating the multi-faceted roles of NPF in fly neuronal activity. Initial literature searches on Drosophila courtship regulators (neurons, genes, channels, pathways) have demonstrated a lack of research on NPF and its receptors. Additionally, Virtual Fly Brain was used to diagram neurons involved with Drosophila courtship and NPF-expression. Experimental evidence hints at a hierarchical role of NPF in Drosophila similar to that of P1 neurons in courtship activity. The current article describes the various NPF-expressing neurons involved with feeding, sleep, and courtship behaviors in Drosophila, diagrams these neurons in a 3D model of the Drosophila brain, and discusses the role of their receptors in Drosophila activity.A lack of database information on NPF expressing neurons highlights the need for more imaging and analysis of NPF neurocircuitry. Findings suggest that NPF is essential to maintaining the balance between sleep, courtship, and feeding behaviors, but further research is necessary to determine the specifics of NPF’s role and relation to NPY.