About

Scott Rifkin is the Principal Investigator of the Rifkin Lab at UC San Diego, which officially began in 2009. His research focuses on the origin of variation, particularly in the context of developmental biology and hybrid inviability. The lab has been supported by multiple NSF grants, including those on transcription factor-DNA interactions and the developmental biology of hybrid inviability. Over the years, the Rifkin Lab has contributed to understanding genetic and molecular mechanisms underlying variation, as evidenced by numerous publications and collaborations. The lab also emphasizes training and mentoring students and postdoctoral fellows across various levels, from high school to graduate students, reflecting a commitment to education and research development in biology.

Research topics

• Biology
• Computer Science
• Genetics
• Artificial Intelligence
• Psychology
• Computational biology
• Botany
• Mathematics
• Cell biology
• Zoology
• Neuroscience
• Evolutionary biology

Selected publications

• Self-Monitoring and Self-Management of Hypertension in US Veterans: A Randomized Controlled Trial

  Journal of the American Society of Nephrology · 2025-10-01

  article
  PublisherDOI

• Simultaneous recording of spikes and calcium signals in odor-evoked responses of <i>Drosophila</i> antennal neurons

  Journal of Neurogenetics · 2025-10-02

  articleOpen access

  ORNs. Calcium imaging showed that homotypic ab2A neurons exhibit similar odor sensitivity, consistent with spike recordings, indicating that a single ORN's response can reliably represent its homotypic counterparts. Furthermore, concurrent dual recordings revealed that peak calcium responses are linearly correlated with spike activity, regardless of imaging site (soma or dendrites), GCaMP variant, odorant, or fly age. These findings validate the use of somatic calcium signals as a reliable proxy for spike activity in fly ORNs and provide a foundation for future large-scale surveys of spike-calcium response relationships across diverse ORN types.

  PublisherOA PDFDOI

• Cell fate ratios are encoded by transcriptional dynamics in the Drosophila retina

  Current Biology · 2025-06-01 · 3 citations

  articleOpen access
  PublisherOA PDFDOI

• Morphological specializations of mosquito CO ₂ -sensing olfactory receptor neurons

  Proceedings of the National Academy of Sciences · 2025-10-23 · 1 citations

  articleOpen access

  Hematophagous mosquitoes use CO 2 as a key arousal signal that gates behavioral responses to host-derived cues. In Aedes aegypti , CO 2 is detected by olfactory receptor neurons (ORNs) housed in the sensory hairs (sensilla) on the maxillary palp. While the molecular mechanism and behavioral significance of CO 2 sensing have been well studied in mosquitoes, the nanoscale three-dimensional structures of their CO 2 -sensing ORNs and associated cells have remained unclear. Using serial block-face scanning electron microscopy, we characterize the CO 2 -sensing cpA neuron and its odor-sensitive neighbors, cpB and cpC, within the capitate sensilla of A. aegypti. Notably, cpA neurons are significantly larger, with an outer dendritic surface area 8 to 12 times greater than that of cpB and cpC neurons. This expanded CO 2 -sensing surface arises from its unique architecture, consisting of numerous flattened dendritic sheets folded into intricate lamellae. In contrast, cpB and cpC dendrites exhibit sparse, narrow cylindrical branches. Moreover, the cpA axon displays a prominent pearls-on-a-string morphology, with numerous mitochondria-rich, nonsynaptic varicosities connected by thin cables. Remarkably, a glial cell and an auxiliary cell together ensheathe the cpA soma but not cpB or cpC, suggesting a specialized role in supporting cpA function. Compared to Drosophila CO 2 -sensitive ORNs, a larger portion of the cpA outer dendrite is embedded within the sensillum cuticle, potentially improving access to environmental CO 2 . These findings reveal key morphological specializations of cpA neurons, thereby advancing our understanding of mosquito sensory biology and laying the groundwork for future studies on the molecular basis and functional ramifications of these anatomical adaptations.

  PublisherDOI

• Hybrid incompatibility emerges at the one-cell stage in interspecies Caenorhabditis embryos

  Current Biology · 2025-07-01 · 1 citations

  articleSenior author
  PublisherDOI

• Simultaneous recording of spikes and calcium signals in odor-evoked responses of <i>Drosophila</i> antennal neurons

  bioRxiv (Cold Spring Harbor Laboratory) · 2025-06-29

  preprintOpen access

  Most insects, including agricultural pests and disease vectors, rely on olfaction for key innate behaviors. Consequently, there is growing interest in studying insect olfaction to gain insights into odor-driven behavior and to support efforts in vector control. Calcium imaging using GCaMP fluorescence is widely used to identify olfactory receptor neurons (ORNs) responsive to ethologically relevant odors. However, accurate interpretation of GCaMP signals in the antenna requires understanding both response uniformity within an ORN population and how calcium signals relate to spike activity. To address this, we optimized a dual-modality recording method combining single-sensillum electrophysiology and widefield imaging for Drosophila ORNs. Calcium imaging showed that homotypic ab2A neurons exhibit similar odor sensitivity, consistent with spike recordings, indicating that a single ORN’s response can reliably represent its homotypic counterparts. Furthermore, concurrent dual recordings revealed that peak calcium responses are linearly correlated with spike activity, regardless of imaging site (soma or dendrites), GCaMP variant, odorant, or fly age. These findings validate the use of somatic calcium signals as a reliable proxy for spike activity in fly ORNs and provide a foundation for future large-scale surveys of spike–calcium response relationships across diverse ORN types.

  PublisherOA PDFDOI

• Hybrid incompatibility emerges at the one-cell stage in interspecies <i>Caenorhabditis</i> embryos

  bioRxiv (Cold Spring Harbor Laboratory) · 2024-10-21 · 3 citations

  preprintOpen accessSenior authorCorresponding

  SUMMARY Intrinsic reproductive isolation occurs when genetic divergence between populations disrupts hybrid development, preventing gene flow and enforcing speciation. 1–4 Over the past two decades, researchers have identified molecular mechanisms underlying a few dozen cases of hybrid incompatibility in animals. 5 Much of this work has focused on mismatches in zygotic gene regulation, 6–11 but other mechanisms have also emerged, including symbiont-driven incompatibilities, 12 nucleoporin mismatches affecting nuclear-cytoplasmic transport, 13 and divergence in centromeric or heterochromatic regions and their regulatory proteins which can lead to the inability of the oocyte cytoplasm to segregate sperm-derived chromosomes. 14–19 Since studies to date have focused on a limited number of species, uncovering mechanisms across diverse taxa will be important to understanding broader patterns of hybrid incompatibility. Here, we investigate the mechanistic basis of hybrid incompatibility in Caenorhabditis nematodes by leveraging the ability of C. brenneri females to produce embryos after mating with males from several other species. We find that incompatibilities emerge between fertilization and the onset of zygotic transcription, which begins at the 4-cell stage. 20–23 In Caenorhabditis embryos, as in many animals, 24,25 sperm deliver chromatin and centrioles into the oocyte. 26–29 After remaining quiescent during oocyte meiosis, the sperm chromatin acquires a nuclear envelope, and centrioles initiate centrosome formation. 30–32 Centrosomes remain tethered to the sperm pronucleus, which positions them near the cortex to establish anterior-posterior polarity. 33,34 We identify two key processes that are destabilized in hybrids: (1) the ability of oocytes to control sperm-derived pronuclear expansion, and (2) successful polar body formation. When sperm pronuclear expansion is delayed, centrosomes detach, which leads to defects in polarity establishment. Hybrid embryos typically experience one or more stochastic failures of early developmental events that accumulate and eventually kill them.

  PublisherDOI

• Dormancy promotes coexistence in fluctuating environments

  Oikos · 2024-10-04 · 1 citations

  articleOpen accessSenior author

  Dormancy allows organisms to survive hostile conditions and is hypothesized to enable species to coexist in fluctuating environments. Although determining how species avoid extinction is critical to understanding the dynamics of natural populations, experimental work exploring if and when dormancy rescues populations from extinction remains rare. We conducted an experiment, where we grew two species of nematode at three temperatures. Strains of Caenorhabditis elegans had mutations altering their propensity to enter a dormant stage and Caenorhabditis briggsae was a single strain with a wildtype background. We used those empirical results to parameterize a model and simulate competitive outcomes in fluctuating environments between the two species. We show that upregulating the dormancy pathway rescues populations that would otherwise go extinct, thereby increasing coexistence between competing species. By leveraging the genetic tools available from a model system, this study provides experimental confirmation that dormancy specifically facilitates species coexistence and thereby promotes diversity. This study system could be used more expansively to explore the role of dormancy in species interactions.

  PublisherOA PDFDOI

• Radiation and diversification of GATA-domain-containing proteins in the genus <i>Caenorhabditis</i>

  bioRxiv (Cold Spring Harbor Laboratory) · 2022-05-21

  preprintOpen accessSenior authorCorresponding

  Abstract Transcription factors are defined by their DNA-binding domains (DBDs). The binding affinities and specificities of a transcription factor to its DNA binding sites can be used by an organism to fine-tune gene regulation and so are targets for evolution. Here we investigate the evolution of GATA-type transcription factors (GATA factors) in the Caenorhabditis genus. Based upon comparisons of their DBDs, these proteins form 13 distinct groups. This protein family experienced a burst of gene duplication in several of these groups along two short branches in the species tree, giving rise to subclades with very distinct complements of GATA factors. By comparing extant gene structures, DBD sequences, genome locations, and selection pressures we reconstructed how these duplications occurred. Although the paralogs have diverged in various ways, the literature shows that at least eight of the DBD groups bind to similar G-A-T-A DNA sequences. Thus, despite gene duplications and divergence among DBD sequences, most Caenorhabditis GATA factors appear to have maintained similar binding preferences, which could create the opportunity for developmental system drift. We hypothesize that this limited divergence in binding specificities contributes to the apparent disconnect between the extensive genomic evolution that has occurred in this genus and the absence of significant anatomical changes.

  PublisherDOI

• Tracking changes in behavioural dynamics using prediction error

  PLoS ONE · 2021 · 5 citations

  Senior authorCorresponding
  • Computer Science
  • Computer Science
  • Artificial Intelligence

  Automated analysis of video can now generate extensive time series of pose and motion in freely-moving organisms. This requires new quantitative tools to characterise behavioural dynamics. For the model roundworm Caenorhabditis elegans, body pose can be accurately quantified from video as coordinates in a single low-dimensional space. We focus on this well-established case as an illustrative example and propose a method to reveal subtle variations in behaviour at high time resolution. Our data-driven method, based on empirical dynamic modeling, quantifies behavioural change as prediction error with respect to a time-delay-embedded 'attractor' of behavioural dynamics. Because this attractor is constructed from a user-specified reference data set, the approach can be tailored to specific behaviours of interest at the individual or group level. We validate the approach by detecting small changes in the movement dynamics of C. elegans at the initiation and completion of delta turns. We then examine an escape response initiated by an aversive stimulus and find that the method can track return to baseline behaviour in individual worms and reveal variations in the escape response between worms. We suggest that this general approach-defining dynamic behaviours using reference attractors and quantifying dynamic changes using prediction error-may be of broad interest and relevance to behavioural researchers working with video-derived time series.

  PublisherOA PDFDOI

Recent grants

• NIH Grant F32GM080966

  NIH · $112k · 2010

• The Developmental Biology of Hybrid Incompatibility

  NSF · $775k · 2020–2024

• Collaborative Research: The Causes of Natural Variation in Protein Expression

  NSF · $339k · 2015–2019

• Dynamics and regulatory logic of the endodermal cell-fate decision in C. elegans

  NIH · $1.4M · 2013–2019

Frequent coauthors

• Sarah R. Stockwell

  University of California, San Diego

  22 shared

• Kevin P. White

  National University of Singapore

  8 shared

• Marinus F. van Batenburg

  Columbia University

  8 shared

• Christian R. Landry

  Université Laval

  7 shared

• Spencer Diamond

  Innovative Genomics Institute

  7 shared

• Erik Saberski

  Scripps Institution of Oceanography

  6 shared

• Arjun Raj

  6 shared

• Harmen J. Bussemaker

  Columbia University

  6 shared

Labs

• Rifkin LabPI

  On the Origin of Variation