Benjamin L. de Bivort, Ph.D. - US grants

Why individuals behave differently from one another is an enduring question in behavioral neuroscience. Every individual is a product of unique genetics, environment, experience and developmental contingencies. How these differences play out to produce individual behavior is currently unknown. This project aims to study the origins of individuality in behavior using the genetic model system Drosophila melanogaster, which permits holding genetics, environment and experience constant across individuals. Nevertheless behavioral diversity on odor-evoked behaviors is abundant in these experimental populations. The molecular and neural circuit mechanisms underlying these individual differences will be investigated using the tools of modern behavioral neuroscience, including high-throughput behavioral testing, pharmacological manipulation to identify critical neuromodulatory effects and neurotransmitters, and imaging to record neural activity. Preliminary evidence suggests that each individual encodes odor information differently. That is, behavioral differences may arise because each individual senses its olfactory environment differently. The mechanisms underlying these differences in stimulus encoding will be the focus of investigation. The principles uncovered are likely applicable in humans as well, given the commonalities of molecular biology across animal species. In order to broadly communicate these principles, and encourage student STEM engagement, the PI will collaborate with the DNA Learning Center of Cold Spring Harbor Laboratory to develop and distribute odor preference kits for high school students. These will allow students to measure variation in their own odor preference and investigate its origin in genetic differences in olfactory receptors.

The objective of this project is to identify the neural underpinnings of the intragenotypic variability in odor-evoked behavior using a uniquely accessible system - the early olfactory circuit of the fruit fly, Drosophila melanogaster. Building on tools developed in their laboratory, a combined approach of behavioral and neurophysiological characterization will be used to determine the: 1) degree of idiosyncrasy in flies' odor preferences, 2) ways in which odor coding varies between individuals, and 3) behavioral consequences of this neurophysiological variation. In flies, the olfactory system is coarsely hardwired, with neurons that are anatomically and genetically identifiable across different individuals. Despite this stereotypy, individual odor preference is quite variable across flies - as in humans. Likewise, the neural coding of odor varies between flies. The relationship between these dimensions of variation is unknown, but can be elucidated by identifying neural coding features that predict behavioral tendencies. First, their behavioral assay will be extended to measure multidimensional odor preferences of individual flies. Second, subcellular-resolution functional imaging will quantify across-fly variation in neural coding in olfactory sub-circuits. Third, these approaches will be combined by recording neural activity in animals that have been first measured for behavioral preferences to assess which idiosyncratic neural activity signals are predictive of idiosyncratic odor preferences.

The NSF Physics of Living Systems (PoLS) Student Research Network (SRN) strives to unite students and faculty working at the interface of physics and biology at different institutions ("nodes") within the US and internationally. A well functioning virtual network could give students at local nodes the ability to take advantage of global educational and research opportunities in PoLS. PoLS is a diverse field, and is composed of researchers and students from varied backgrounds. No single institution can offer (1) the breadth and depth of research and (2) courses that both cover the relevant intellectual landscape and provide in-depth training for students. Such training is critical to create the next generation of researchers who can contribute quantitatively to biophysics, with the ability to move between biology, physics, mathematics, and engineering; PoLS students have important roles to play in this next generation. In addition, no single institution has the range of equipment needed to study PoLS on the enormous range of time and length scales encountered in biological systems. Finally, few single institutions can fruitfully integrate science and engineering to inspire biomedical, robotic and prosthetic devices that will result from basic PoLS research. The HF-SRN will create an environment for students in which they can work among various disciplines while maintaining the physics mindset (simplified systems, few parameter predictive models) and developing new physics. This network will train students (paraphrasing Philip Nelson in his 2008 Biological Physics textbook) "who can switch fluidly between both kinds of brain: the `developmental/historical/complex' sciences and the 'universal/ahistorical/reductionist'." As significant collaborative and educational flux develops within the HF-SRN, successful activities will be broadened to the other US nodes (ultimately with the expectation to engage PoLS SRN international partners). The evaluation plan will help guide aspects of the HF-SRN that could increase flux in other programs in the NSF Science Across Virtual Institutes initiative. More broadly, PoLS SRN students can be leaders in the next generation of researchers who blend biology and physics research seamlessly. Such students will create materials which will seed future K-12 as well as university PoLS curricula. Efforts will be made to extend the educational and research efforts developed within the HF-SRN (and entire SRN) to a broader community including local minority serving institutions. Advances in PoLS can lead to advances in applications such as genome editing, cancer dynamics, robotics and human-assist devices, among others.

During the last period of funding as part of the SRN, the Georgia Tech, Harvard and Maryland nodes have advanced their respective PoLS programs, developing cohesive local communities. The goal of this project is to further develop opportunities for students (and their ideas) to "flow" more easily within the SRN and thereby discover working principles of increased human network flux that can be transferred into the larger SRN. To do so, significant interactions (and evaluations of those interactions) will be developed among three existing SRN nodes (adding Emory as a subcontract to Georgia Tech), forming a "High Flux SRN" (HF-SRN). The HF-SRN will engage in activities such as 1) Collaborative Focused Research Projects, which span nodes and are "built to succeed" by leveraging student and faculty expertise in current projects; 2) Student-Led Dynamic Working Groups (e.g., in biomolecular, microbial, cellular and organismal physics) leveraging faculty research strengths and student interest to develop cross-node communities for these topics. 3) Student-Led Bootcamps: intense 2-3 day tutorials (e.g., microscopy, robophysics, image analysis) with cross-subgroup cutting themes, open to HF-SRN members and held at a particular node; 4) Student-Led Workshops: composed of talks, poster and discussion sessions, inviting the entire PoLS SRN; 5) Curriculum development via open-source course materials, integrating complementary expertise across nodes. All activities will be evaluated and assessed by a Council composed of the lead PIs at each node. This project is being jointly supported by the Physics of Living Systems program in the Division of Physics, the Molecular Biophysics Program in the Division of Molecular and Cellular Biosciences, and the Modulation Program in the Division of Integrative Organismal Systems.

This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.