About

William Sullivan is a Distinguished Professor of Molecular, Cell & Developmental Biology at UCSC. He holds a B.A. from the University of California, San Diego, and a Ph.D. from the University of Washington, Seattle, with postdoctoral training at the University of California, San Francisco. His research focuses on the structural and regulatory mechanisms that drive cell division, particularly the processes involved in furrow ingression during cytokinesis and its coordination with chromosome segregation and other mitotic events. His lab employs molecular genetic and cellular approaches to understand how membrane addition via vesicles from recycling endosomes contributes to furrow formation, and how actin remodelers are recruited to facilitate this process. Current efforts include investigating the role of vesicle-mediated membrane addition in controlling furrow timing and positioning, the mechanisms of F-actin recruitment to the cleavage furrow, and the signaling pathways regulating membrane addition during the cell cycle. In addition to cell division, Sullivan's lab studies host/pathogen interactions, with a focus on Wolbachia, obligate intracellular bacterial endosymbionts found in over 60% of insect species and present in worms. His research aims to understand how Wolbachia manipulate host cell processes to facilitate transmission during mitosis and how they regulate their replication within host cells. The lab has developed high-throughput cell-based assays to identify potent Wolbachia-specific antibiotics, contributing to efforts against African River Blindness caused by Wolbachia-infected nematodes.

Research topics

• Biology
• Genetics
• Evolutionary biology
• Cell biology
• Chemistry
• Nuclear physics
• Aerospace engineering
• Engineering
• Physics
• Computational biology
• Biophysics
• Medicine
• Virology
• Microbiology

Selected publications

• Wolbachia-induced Cytoplasmic Incompatibility drives epigenetic and maternally-influenced post-embryonic defects

  bioRxiv (Cold Spring Harbor Laboratory) · 2026-04-16

  articleOpen accessSenior author

  A common form of Wolbachia-induced manipulation of host reproduction is Cytoplasmic Incompatibility (CI). In CI, Wolbachia modification of sperm results in pronounced defects in paternal chromosome condensation, replication, and segregation during the first mitotic division. Recent studies in D. simulans demonstrate that CI also induces independent and distinct later developmental defects resulting in high rates of mitotic errors during the mid-blastula transition and larval lethality. Here we show that in D. melanogaster, embryos derived from CI crosses experienced significant mitotic defects during gastrulation and increased larval lethality, both of which were eliminated in the progeny of Rescue crosses (both sexes infected). Examination of CI using females from 13 genetically distinct wild-type lines of the Drosophila Genetic Reference Panel (DGRP) revealed significant variation in the strength of the CI-induced lethality. Early embryonic pre-hatching and late larval lethal phases were uncorrelated, suggesting distinct factors influence the extent of the two lethal phases. Additionally, 3rd instar larvae and adults derived from D. melanogaster CI crosses exhibited locomotor defects that were also eliminated in Rescue crosses. These studies support a model in which Wolbachia effects on the sperm chromatin produce delayed developmental and locomotor defects, suggesting the involvement of epigenetic mechanisms. Support for this idea comes from our finding that levels of the heritable chromatin mark H3K27me1 are significantly elevated in CI-derived embryos. We conclude that the full measure of CI strength should take into account pre- and post-hatching lethality as well as locomotor defects. Together our findings suggest that the strength of these CI-induced phenotypes is governed at least in part by epigenetics and the maternal genetic background.

  PublisherOA PDFDOI

• Wolbachia-induced Cytoplasmic Incompatibility drives epigenetic and maternally-influenced post-embryonic defects

  PLoS Pathogens · 2026-05-07

  articleOpen accessSenior author

  A common form of Wolbachia-induced manipulation of host reproduction is Cytoplasmic Incompatibility (CI). In CI, Wolbachia modification of sperm results in pronounced defects in paternal chromosome condensation, replication, and segregation during the first mitotic division. Recent studies in D. simulans demonstrate that CI also induces independent and distinct later developmental defects resulting in high rates of mitotic errors during the mid-blastula transition and larval lethality. Here we show that in D. melanogaster, embryos derived from CI crosses experienced significant mitotic defects during gastrulation and increased larval lethality, both of which were eliminated in the progeny of Rescue crosses (both sexes infected). Examination of CI using females from 13 genetically distinct wild-type lines of the Drosophila Genetic Reference Panel (DGRP) revealed significant variation in the strength of the CI-induced lethality. Early embryonic pre-hatching and late larval lethal phases were uncorrelated, suggesting distinct factors influence the extent of the two lethal phases. Additionally, 3rd instar larvae and adults derived from D. melanogaster CI crosses exhibited locomotor defects that were also eliminated in Rescue crosses. These studies support a model in which Wolbachia effects on the sperm chromatin produce delayed developmental and locomotor defects, suggesting the involvement of epigenetic mechanisms. Support for this idea comes from our finding that levels of the heritable chromatin mark H3K27me1 are significantly elevated in CI-derived embryos. We conclude that the full measure of CI strength should take into account pre- and post-hatching lethality as well as locomotor defects. Together our findings suggest that the strength of these CI-induced phenotypes is governed at least in part by epigenetics and the maternal genetic background.

  PublisherDOI

• Wolbachia-mediated reduction in the glutamate receptor mGluR promotes female promiscuity and bacterial spread

  Cell Reports · 2025-05-01 · 3 citations

  articleOpen accessSenior author

  The molecular mechanisms by which parasites mediate host behavioral changes remain largely unexplored. Here, we examine Drosophila melanogaster infected with Wolbachia, a symbiont transmitted through the maternal germline, and find Wolbachia infection increases female receptivity to male courtship and hybrid mating. Wolbachia colonize regions of the brain that control sense perception and behavior. Quantitative global proteomics identify 177 differentially abundant proteins in infected female larval brains. Genetic alteration of the levels of three of these proteins in adults, the metabotropic glutamate receptor mGluR, the transcription factor TfAP-2, and the odorant binding protein Obp99b, each mimic the effect of Wolbachia on female receptivity. Furthermore, >700 Wolbachia proteins are detected in infected brains. Through abundance and molecular modeling analyses, we distinguish several Wolbachia-produced proteins as potential effectors. These results identify potential networks of host and Wolbachia proteins that modify behavior to promote mating success and aid the spread of Wolbachia.

  PublisherOA PDFDOI

• Fexinidazole and Corallopyronin A target Wolbachia-infected sheath cells present in filarial nematodes

  PLoS Pathogens · 2025-09-08 · 1 citations

  articleOpen accessSenior authorCorresponding

  The discovery of the endosymbiotic bacteria Wolbachia as an obligate symbiont of. filarial nematodes has led to antibiotic-based treatments for filarial diseases. While lab. and clinical studies have yielded promising results, recent animal studies revealed that Wolbachia levels rebound following treatment with the antibiotic rifampicin. Previous work revealed that a potential source of the bacterial rebound in female worms were dense clusters of Wolbachia in ovarian tissue. The number, size, and density of these Wolbachia clusters were not diminished despite antibiotic treatment. Here we define the cellular characteristics of the Wolbachia clusters in Brugia pahangi (wBp) and identify drugs that target them. We show that the Wolbachia clusters originate from newly formed sheath cells adjacent to the distal tip cell. The dramatically enlarged volume of a Wolbachia-infected sheath cell is strikingly similar to endosymbiont-induced bacteriocytes found in many insect species. Ultrastructural analysis reveals that the clustered Wolbachia present within the sheath cells have a distinct morphology from those present within the oocytes, and that the sheath cell membrane appears to have interdigitations with the adjacent oocyte membrane. This includes membrane-based channels that provide a connection between Wolbachia-infected sheath cells and oocytes. We determined that the Wolbachia within the sheath cells are either quiescent or replicating at a very low rate. Screens of 11 known antibiotics and other drugs revealed that Fexinidazole, Corallopyronin A and Rapamycin reduced the number of Wolbachia clusters infecting sheath cells but only Fexinidazole and Corallopyronin A showed a highly significant difference (p < 0.0001) compared to the control group.

  PublisherOA PDFDOI

• Fexinidazole and Corallopyronin A target <i>Wolbachia</i> -infected sheath cells present in filarial nematodes

  bioRxiv (Cold Spring Harbor Laboratory) · 2025-01-26

  preprintOpen accessSenior authorCorresponding

  Summary The discovery of the endosymbiotic bacteria Wolbachia as an obligate symbiont of filarial nematodes has led to antibiotic-based treatments for filarial diseases. While lab and clinical studies have yielded promising results, recent animal studies reveal that Wolbachia levels may rebound following treatment with suboptimal doses of the antibiotic rifampicin. Previous work showed that a likely source of the bacterial rebound in females were dense clusters of Wolbachia in ovarian tissue. The number, size, and density of these Wolbachia clusters were not diminished despite antibiotic treatment. Here we define the cellular characteristics of the Wolbachia clusters in Brugia pahangi (wBp) and identify drugs that also target them. We have evidence that the Wolbachia clusters originate from newly formed sheath cells adjacent to the ovarian Distal Tip Cells. The dramatically enlarged volume of an infected sheath cell is strikingly similar to endosymbiont-induced bacteriocytes found in many insect species. Ultrastructural analysis reveals that the clustered Wolbachia present within the sheath cells exhibit a distinct morphology and form direct connections with the oocyte membrane and possibly the cytoplasm. This includes membrane-based channels providing a connection between Wolbachia -infected sheath cells and oocytes. We also determined that the Wolbachia within the sheath cells are either quiescent or replicating at a very low rate. Screens of known antibiotics and other drugs revealed that two drugs, Fexinidazole and Corallopyronin A, significantly reduced the number of clustered Wolbachia located within the sheath cells.

  PublisherOA PDFDOI

• Quantification of variegated <i>Drosophila</i> ommatidia with high-resolution image analysis and machine learning

  Biology Methods and Protocols · 2025-01-01

  articleOpen access

  Abstract A longstanding challenge in biology is accurately analyzing images acquired using microscopy. Recently, machine learning (ML) approaches have facilitated detailed quantification of images that were refractile to traditional computation methods. Here, we detail a method for measuring pigments in the complex-mosaic adult Drosophila eye using high-resolution photographs and the pixel classifier ilastik [1]. We compare our results to analyses focused on pigment biochemistry and subjective interpretation, demonstrating general overlap, while highlighting the inverse relationship between accuracy and high-throughput capability of each approach. Notably, no coding experience is necessary for image analysis and pigment quantification. When considering time, resolution, and accuracy, our view is that ML-based image analysis is the preferred method.

  PublisherOA PDFDOI

• Remarkable chromosomes and karyotypes: A top 10 list

  Molecular Biology of the Cell · 2024-03-22 · 1 citations

  articleOpen access1st authorCorresponding

  Chromosomes and karyotypes are particularly rich in oddities and extremes. Described below are 10 remarkable chromosomes and karyotypes sprinkled throughout the tree of life. These include variants in chromosome number, structure, and dynamics both natural and engineered. This versatility highlights the robustness and tolerance of the mitotic and meiotic machinery to dramatic changes in chromosome and karyotype architecture. These examples also illustrate that the robustness comes at a cost, enabling the evolution of chromosomes that subvert mitosis and meiosis.

  PublisherOA PDFDOI

• Clarifying Mendelian vs non-Mendelian inheritance

  Genetics · 2024-05-28 · 12 citations

  articleOpen accessSenior author

  Gregor Mendel developed the principles of segregation and independent assortment in the mid-1800s based on his detailed analysis of several traits in pea plants. Those principles, now called Mendel's laws, in fact, explain the behavior of genes and alleles during meiosis and are now understood to underlie "Mendelian inheritance" of a wide range of traits and diseases across organisms. When asked to give examples of inheritance that do NOT follow Mendel's laws, in other words, examples of non-Mendelian inheritance, students sometimes list incomplete dominance, codominance, multiple alleles, sex-linked traits, and multigene traits and cite as their sources the Khan Academy, Wikipedia, and other online sites. Against this background, the goals of this Perspective are to (1) explain to students, healthcare workers, and other stakeholders why the examples above, in fact, display Mendelian inheritance, as they obey Mendel's laws of segregation and independent assortment, even though they do not produce classic Mendelian phenotypic ratios and (2) urge individuals with an intimate knowledge of genetic principles to monitor the accuracy of learning resources and work with us and those resources to correct information that is misleading.

  PublisherDOI

• Acentric chromosome congression and alignment on the metaphase plate via kinetochore-independent forces

  Genetics · 2024-11-18

  articleOpen accessSenior author

  Chromosome congression and alignment on the metaphase plate involves lateral and microtubule plus-end interactions with the kinetochore. Here we take advantage of our ability to efficiently generate a GFP-marked acentric X chromosome fragment in Drosophila neuroblasts to identify forces acting on chromosome arms that drive congression and alignment. We find acentrics efficiently congress and align on the metaphase plate, often more rapidly than kinetochore-bearing chromosomes. Unlike intact chromosomes, the paired sister acentrics oscillate as they move to and reside on the metaphase plate in a plane distinct and significantly further from the main mass of intact chromosomes. Consequently, at anaphase onset, acentrics are oriented either parallel or perpendicular to the spindle. Parallel-oriented sisters separate by sliding while those oriented perpendicularly separate via unzipping. This oscillation, together with the fact that in the presence of spindles with disrupted interpolar microtubules acentrics are rapidly shunted away from the poles, indicates that distributed plus-end-directed forces are primarily responsible for acentric migration. This conclusion is supported by the observation that reduction of EB1 preferentially disrupts acentric alignment. Taken together, these studies suggest that plus-end forces mediated by the outer interpolar microtubules contribute significantly to acentric congression and alignment. Surprisingly, we observe disrupted telomere pairing and alignment of sister acentrics indicating that the kinetochore is required to ensure proper gene-to-gene alignment of sister chromatids. Finally, we demonstrate that like mammalian cells, the Drosophila congressed chromosomes on occasion exhibit a toroid configuration.

  PublisherOA PDFDOI

• Acentric chromosome congression and alignment on the metaphase plate via kinetochore-independent forces in <i>Drosophila</i>

  bioRxiv (Cold Spring Harbor Laboratory) · 2023-11-16

  preprintOpen accessSenior author

  neuroblasts to identify forces acting on chromosome arms that drive congression and alignment. We find acentrics efficiently align on the metaphase plate, often more rapidly than kinetochore-bearing chromosomes. Unlike intact chromosomes, the paired sister acentrics oscillate as they move to and reside on the metaphase plate in a plane distinct and significantly further from the main mass of intact chromosomes. Consequently, at anaphase onset acentrics are oriented either parallel or perpendicular to the spindle. Parallel-oriented sisters separate by sliding while those oriented perpendicularly separate via unzipping. This oscillation, together with the fact that in monopolar spindles acentrics are rapidly shunted away from the poles, indicates that distributed plus-end directed forces are primarily responsible for acentric migration. This conclusion is supported by the observation that reduction of EB1 preferentially disrupts acentric alignment. In addition, reduction of Klp3a activity, a gene required for the establishment of pole-to-pole microtubules, preferentially disrupts acentric alignment. Taken together these studies suggest that plus-end forces mediated by the outer pole-to-pole microtubules are primarily responsible for acentric metaphase alignment. Surprisingly, we find that a small fraction of sister acentrics are anti-parallel aligned indicating that the kinetochore is required to ensure parallel alignment of sister chromatids. Finally, we find induction of acentric chromosome fragments results in a global reorganization of the congressed chromosomes into a torus configuration. Article Summary: The kinetochore serves as a site for attaching microtubules and allows for successful alignment, separation, and segregation of replicated sister chromosomes during cell division. However, previous studies have revealed that sister chromosomes without kinetochores (acentrics) often align to the metaphase plate, undergo separation and segregation, and are properly transmitted to daughter cells. In this study, we discuss the forces acting on chromosomes, independent of the kinetochore, underlying their successful alignment in early mitosis.

  PublisherOA PDFDOI

Recent grants

• Mitotic transmission of acentric chromosomes

  NIH · $2.5M · 2021–2030

• High-throughput screen targeting Wolbachia to combat filarial diseases

  NIH · $851k · 2014–2017

• Collaborative Research: How does an intracellular symbiont manipulate host cell biology?

  NSF · $271k · 2015–2020

• Cytokinesis in the early Drosophila embryo

  NIH · $5.2M · 1991–2016

• Mechanisms of Acentric Chromosome Transmission

  NIH · $1.4M · 2017–2022

Frequent coauthors

• Alain Debec

  Université Paris-Est Créteil

  20 shared

• Wendy F. Rothwell

  15 shared

• Brandt Warecki

  University of California, Santa Cruz

  14 shared

• Frédéric Landmann

  Centre de Recherche en Biologie cellulaire de Montpellier

  14 shared

• Laura Chappell

  University of California, Santa Cruz

  14 shared

• Anne Royou

  Université de Bordeaux

  12 shared

• Justin Crest

  Stanford University

  11 shared

• Makedonka Mitreva

  James S. McDonnell Foundation

  9 shared

Labs

• The Sullivan LabPI