Douglas Portman

Douglas Portman

Professor

PhD

Research Active

Now accepting:

PhD students

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Office Location
2-9647 KMRB
Telephone
(585) 275-7414
Web Address
Website

Research Overview

Genes, Circuits, and Behavior: Biological Sex as a Modulator of Neuronal Circuit Development and Function

Biological sex is a fundamental variable in the development and function of the nervous system. Across species, sex differences in behavior and brain function can reveal how genetic programs can produce flexibility within conserved neural circuits. In humans, many neurological and neuropsychiatric disorders differ by sex in incidence or severity, raising the possibility that sex-based mechanisms of susceptibility or resilience could inform new strategies for prevention, diagnosis, and treatment.

We use the nematode C. elegans to study how biological sex shapes neural circuit function and behavior. The compact and fully mapped nervous system of C. elegans enables mechanistic dissection of these processes at cellular and molecular resolution. The two sexes of this species, males and hermaphrodites, differ dramatically in their behaviors and life strategies — for example, hermaphrodites prioritize feeding, while males will abandon food in search of mates. We and others have found that many of these behavioral differences arise not from dedicated sex-specific circuits, but from the sex-dependent modulation of neurons and circuits shared by both sexes.

An important finding from our work is that that biological sex can reconfigure the physiology of sex-shared neurons to optimize behavior in a sex-specific context. This modulation occurs at multiple levels: it can reshape sensory tuning to prioritize detection of sex- or context-relevant sensory cues (such as food or pheromones), and it can reorganize neuromodulatory pathways that govern behavioral states and prioritization.

Our current work focuses on two related problems. First, we are working to identify molecular pathways and cellular mechanismsthrough which sex, developmental stage, and physiological state converge to regulate shared neural circuits. Second, we seek to understand how and why targeting certain regulatory nodes — e.g., sensory neurons and neuromodulators — enables adaptive sex differences in behavior. Our studies provide a framework for dissecting how multiple dimensions of internal state are integrated at the level of individual neurons to produce adaptive behavioral variation — a problem at the heart of both evolutionary neurobiology and human brain health.

 

Research Interests

  • Genetics of development and behavior in C. elegans
  • Neural cell fate specification
  • Sex differences in neural circuit function
  • Sexual dimorphism in developmental patterning

Selected Publications

  • Luo J, Barrios A, and Portman DS. (2024) elegans males optimize mate-choice decisions via sex-specific responses to multimodal sensory cues. Current Biology 34, 1309-1323. PMID: 38471505. doi: 10.1016/j.cub.2024.02.036
  • Burkhardt RN, Artyukhin AB, Aprison EZ, Curtis BJ, Fox BW, Ludewig AH, Palomino DF, Luo J, Chaturbedi A, Panda O, Wrobel CJJ, Baumann V, Portman DS, Lee SS, Ruvinsky I, and Schroeder FC. (2023) Sex-specificity of the elegans metabolome. Nature Communications 14, 320. PMID: 36658169. doi: 10.1038/s41467-023-36040-y
  • Pechuk V, Goldman G, Salzberg Y, Chaubey AH, Bola RA, Hoffman JR, Endreson ML, Miller RM, Reger NJ, Portman DS, Ferkey DM, Schneidman E, Oren-Suissa M. (2022) Reprogramming the topology of the nociceptive circuit in elegans reshapes sexual behavior. Current Biology 32, 4372-4385. PMID: 36075218. doi: 10.1016/j.cub.2022.08.038
  • Luo J and Portman DS. (2021) Sex-specific, pdfr-1-dependent modulation of pheromone avoidance by food abundance enables flexibility in elegans foraging behavior. Current Biology 31, 4449-4461. PMID 34437843. doi: 10.1016/j.cub.2021.07.069
  • Lawson H, Wexler LR, Wnuk HK, and Portman DS. (2020) Dynamic, non-binary specification of sexual state in the elegans nervous system. Current Biology 30, 3617-3623. PMID: 32707065. doi: 10.1016/j.cub.2020.07.007
  • Wexler LR, Miller RM, and Portman DS. (2020) elegans males integrate food signals and biological sex to modulate state-dependent chemosensation and behavioral prioritization. Current Biology 30, 2695-2706. PMID: 32531276. doi: 10.1016/j.cub.2020.05.006
  • Lawson HN, Vuong E, Miller RM, Kiontke K, Fitch DHA, and Portman DS. (2019) The Makorin lep-2 and the lncRNA lep-5 regulate lin-28 to schedule sexual maturation of the elegans nervous system. eLife 8, e43660. PMID: 31264582. doi: 10.7554/eLife.43660
  • Kiontke KE, Herrera A, Vuong E, Luo J, Fitch DHA*, and Portman DS*. (2019) The long non-coding RNA lep-5 promotes the juvenile-to-adult transition by stabilizing LIN-28. Dev Cell 49, 542-555. PMID: 30956008. doi: 10.1016/j.devcel.2019.03.003 *co-corresponding authors.
  • Pereira L, Aeschimann F, Wang C, Lawson H, Serrano-Saiz E, Portman DS, Großhans H, and Hobert O. (2019) Timing mechanism of sexually dimorphic nervous system differentiation. eLife 8, e42078. PMID: 30599092. doi: 10.7554/eLife.42078
  • Fagan K, Luo J, Lagoy RC, Schroeder FC, Albrecht DR, and Portman DS. (2018) A single-neuron chemosensory switch determines the valence of a sexually dimorphic sensory behavior. Current Biology 28, 902-914. PMID: 29558638. doi: 10.1016/j.cub.2018.02.029
  • Ryan DA, Miller RM, Lee KH, Neal SJ, Fagan KA, Sengupta P, and Portman DS. (2014) Sex, age and hunger regulate behavioral prioritization through dynamic modulation of chemoreceptor expression. Current Biology 24, 2509-17. PMID: 25438941. doi: 10.1016/j.cub.2014.09.032