About

Ethan Bier is a professor at the UC San Diego School of Biological Sciences with a research focus on developmental patterning and using Drosophila as a model to understand human disease processes. His work in developmental studies has long-standing interest in how graded BMP signaling establishes cell fates along the dorsal-ventral axis of Drosophila embryos and how wing vein formation occurs along borders between discrete domains in the wing imaginal disc. His research includes cloning the short gastrulation (sog) gene, which encodes a secreted BMP antagonist homologous to vertebrate Chordin, and demonstrating the conservation of sog activity in Xenopus embryos. His studies have revealed mechanisms by which BMP activity gradients are formed and visualized, involving diffusion, degradation, and endocytosis, and how these gradients influence dorsal and lateral CNS patterning in flies and zebrafish. Bier's work on wing vein patterning investigates how primary positional information from BMP and Hedgehog gradients is refined into sharp borders to define vein development, as well as the evolution of gene regulatory networks underlying wing development in different dipteral species. His research also extends to using Drosophila to study human diseases, identifying genetic pathways involved in conditions such as Angelman syndrome, Alzheimer's disease, congenital heart defects, and metabolic disorders. His collaborative projects include examining the effects of bacterial and viral toxins on cellular trafficking and barrier integrity, with implications for diseases involving epithelial or endothelial permeability. Additionally, Bier has developed quantitative imaging and genome analysis tools to study gene expression patterns and pattern formation in development, contributing to models that explain how gene length influences morphogen-dependent patterning.

Research topics

• Genetics
• Biology
• Ecology
• Computational biology
• Immunology
• Risk analysis (engineering)
• Business
• Neuroscience
• Biotechnology
• Evolutionary biology
• Medicine

Selected publications

• Driving a protective allele of the mosquito FREP1 gene to combat malaria

  Nature · 2025-07-23 · 9 citations

  articleOpen accessSenior author

  Abstract Malaria remains a substantial global health challenge, causing approximately half a million deaths each year 1 . The mosquito fibrinogen-related protein 1 (FREP1) is required for malaria parasites to infect the midgut epithelium 2 . The naturally occurring FREP1 Q allele has been reported to prevent parasite infection, while supporting essential physiological functions in the mosquito 3 . Here we generate congenic strains of Anopheles stephensi , edited to carry either the parasite-susceptible FREP1 L224 or the putative-refractory FREP1 Q224 alleles. The FREP1 Q224 allele confers robust resistance to infection by both human and rodent malaria parasites, with negligible fitness costs. The protective FREP1 Q224 allele can be efficiently driven into FREP1 L224 mosquito populations using a novel linked allelic-drive system that selectively replaces the L224 codon with the parasite-refractory Q224 allele, thereby rendering populations refractory to parasite infection. This antimalaria drive system provides a novel genetic approach to aid in malaria elimination efforts.

  PublisherOA PDFDOI

• Developmental progression of DNA double-strand break repair deciphered by a single-allele resolution mutation classifier

  Nature Communications · 2024-03-23 · 9 citations

  articleOpen accessSenior author

  DNA double-strand breaks (DSBs) are repaired by a hierarchically regulated network of pathways. Factors influencing the choice of particular repair pathways, however remain poorly characterized. Here we develop an Integrated Classification Pipeline (ICP) to decompose and categorize CRISPR/Cas9 generated mutations on genomic target sites in complex multicellular insects. The ICP outputs graphic rank ordered classifications of mutant alleles to visualize discriminating DSB repair fingerprints generated from different target sites and alternative inheritance patterns of CRISPR components. We uncover highly reproducible lineage-specific mutation fingerprints in individual organisms and a developmental progression wherein Microhomology-Mediated End-Joining (MMEJ) or Insertion events predominate during early rapid mitotic cell cycles, switching to distinct subsets of Non-Homologous End-Joining (NHEJ) alleles, and then to Homology-Directed Repair (HDR)-based gene conversion. These repair signatures enable marker-free tracking of specific mutations in dynamic populations, including NHEJ and HDR events within the same samples, for in-depth analysis of diverse gene editing events.

  PublisherOA PDFDOI

• Gene Editing in the Chagas Disease Vector <i>Rhodnius prolixus</i> by Cas9-Mediated ReMOT Control

  The CRISPR Journal · 2024-04-01 · 19 citations

  articleOpen access

  Rhodnius prolixus is currently the model vector of choice for studying Chagas disease transmission, a debilitating disease caused by Trypanosoma cruzi parasites. However, transgenesis and gene editing protocols to advance the field are still lacking. Here, we tested protocols for the maternal delivery of CRISPR-Cas9 (clustered regularly spaced palindromic repeats/Cas-9 associated) elements to developing R. prolixus oocytes and strategies for the identification of insertions and deletions (indels) in target loci of resulting gene-edited generation zero (G0) nymphs. We demonstrate successful gene editing of the eye color markers Rp-scarlet and Rp-white , and the cuticle color marker Rp-yellow, with highest effectiveness obtained using Receptor-Mediated Ovary Transduction of Cargo (ReMOT Control) with the ovary-targeting BtKV ligand. These results provide proof of concepts for generating somatic mutations in R. prolixus and potentially for generating germ line-edited lines in triatomines, laying the foundation for gene editing protocols that could lead to the development of novel control strategies for vectors of Chagas disease.

  PublisherOA PDFDOI

• A self-eliminating allelic-drive reverses insecticide resistance in Drosophila leaving no transgene in the population

  Nature Communications · 2024-11-17 · 8 citations

  articleOpen accessSenior author

  Insecticide resistance (IR) poses a significant global challenge to public health and welfare. Here, we develop a locally-acting unitary self-eliminating allelic-drive system, inserted into the Drosophila melanogaster yellow (y) locus. The drive cassette encodes both Cas9 and a single gRNA to bias inheritance of the favored wild-type (1014 L) allele over the IR (1014 F) variant of the voltage-gated sodium ion channel (vgsc) target locus. When enduring a fitness cost, this transiently-acting drive can increase the frequency of the wild-type allele to 100%, depending on its seeding ratio, before being eliminated from the population. However, in a fitness-neutral "hover" mode, the drive maintains a constant frequency in the population, completely converting IR alleles to wild-type, even at low initial seeding ratios.

  PublisherOA PDFDOI

• Author Correction: tgCRISPRi: efficient gene knock-down using truncated gRNAs and catalytically active Cas9

  Nature Communications · 2024-04-12

  erratumOpen accessSenior authorCorresponding
  PublisherOA PDFDOI

• Conceptual risk assessment of mosquito population modification gene-drive systems to control malaria transmission: preliminary hazards list workshops

  Frontiers in Bioengineering and Biotechnology · 2023-10-26 · 9 citations

  articleOpen access

  The field-testing and eventual adoption of genetically-engineered mosquitoes (GEMs) to control vector-borne pathogen transmission will require them meeting safety criteria specified by regulatory authorities in regions where the technology is being considered for use and other locales that might be impacted. Preliminary risk considerations by researchers and developers may be useful for planning the baseline data collection and field research used to address the anticipated safety concerns. Part of this process is to identify potential hazards (defined as the inherent ability of an entity to cause harm) and their harms, and then chart the pathways to harm and evaluate their probability as part of a risk assessment. The University of California Malaria Initiative (UCMI) participated in a series of workshops held to identify potential hazards specific to mosquito population modification strains carrying gene-drive systems coupled to anti-parasite effector genes and their use in a hypothetical island field trial. The hazards identified were placed within the broader context of previous efforts discussed in the scientific literature. Five risk areas were considered i) pathogens, infections and diseases, and the impacts of GEMs on human and animal health, ii) invasiveness and persistence of GEMs, and interactions of GEMs with target organisms, iii) interactions of GEMs with non-target organisms including horizontal gene transfer, iv) impacts of techniques used for the management of GEMs and v) evolutionary and stability considerations. A preliminary hazards list (PHL) was developed and is made available here. This PHL is useful for internal project risk evaluation and is available to regulators at prospective field sites. UCMI project scientists affirm that the subsequent processes associated with the comprehensive risk assessment for the application of this technology should be driven by the stakeholders at the proposed field site and areas that could be affected by this intervention strategy.

  PublisherOA PDFDOI

• Gene editing in the Chagas disease vector <i>Rhodnius prolixus</i> by Cas9-mediated ReMOT Control

  bioRxiv (Cold Spring Harbor Laboratory) · 2023-08-15 · 2 citations

  preprintOpen access

  Abstract Rhodnius prolixus is currently the model vector of choice for studying Chagas disease transmission, a debilitating disease caused by Trypanosoma cruzi parasites. Despite the broad use of double-stranded RNA interference for the knockdown of gene function in R. prolixus , transgenesis and gene editing protocols are still lacking. Here we tested Receptor-Mediated Ovary Transduction of Cargo (ReMOT Control) and direct parental injection of CRISPR (DIPA-CRISPR) for the maternal delivery of CRISPR/Cas9 elements to developing R. prolixus oocytes, and strategies for the identification of insertions/deletions (indels) in target loci of resulting gene-edited G0 nymphs. We demonstrate successful ReMOT Control-mediated gene editing of the eye color markers Rp-scarlet and Rp-white , and the cuticle color marker Rp-yellow, with highest effectiveness obtained using the ovary-targeting BtKV ligand. These results provide proof-of-concepts for generating somatic mutations in R. prolixus and potentially for generating germline edited lines in triatomines. Our studies also suggest that optimal strategies for recovery of mutations include performing multiple gRNA injections and the use of visible phenotypes such as those displayed in the Rp-scarlet, Rp-white and Rp-yellow loci for future Co-CRISPR experiments. These results will lay the foundation for gene editing protocols for triatomines and could lead to the development of novel control strategies for vectors of Chagas disease. Author Summary Rhodnius prolixus is an insect vector of the protozoan Trypanossoma cruzi , causative agent of debilitating Chagas disease. To fight the spread of the disease, it has been suggested that biological control of the insect should be attempted. Gene editing by the novel CRISPR methodology holds great promise in this sense, as it enables to target almost any gene in the genome for mutagenesis, thus allowing the control of insect physiology and reproduction. Here we have tested protocols for the delivery of CRISPR reagents as an attempt to enable genome editing of the vector. Our results show that maternal delivery of CRISPR by the ReMOT Control method is efficient for mutating eye and cuticle color genes in the resulting nymphs, generating edited animals with red eyes, white eyes or a yellow cuticle. This is the first report of gene editing in a vector of Chagas disease and should lay the basis to produce modified animals either unable to carry the T. cruzi parasite or to reproduce.

  PublisherOA PDFDOI

• Development of an anti-Pfs230 monoclonal antibody as a Plasmodium falciparum gametocyte blocker

  Research Square · 2023-12-19

  preprintOpen accessSenior authorCorresponding

  Abstract Vector control is a crucial strategy for malaria elimination by preventing infection and reducing disease transmission. Most gains have been achieved through insecticide-treated nets (ITNs) and indoor residual spraying (IRS), but the emergence of insecticide resistance among Anopheles mosquitoes calls for new tools to be applied. Here, we present the development of a highly effective murine monoclonal antibody, targeting the N-terminal region of the Plasmodium falciparum gametocyte antigen Pfs230, that can decrease the infection prevalence by &gt; 50% when fed to Anopheles mosquitoes with gametocytes in an artificial membrane feeding system. We used a standard mouse immunization protocol followed by protein interaction and parasite-blocking validation at three distinct stages of the monoclonal antibody development pipeline: post-immunization, post-hybridoma generation, and final validation of the monoclonal antibody. We evaluated twenty antibodies identifying one (mAb 13G9) with high Pfs230-affinity and parasite-blocking activity. This 13G9 monoclonal antibody could potentially be developed into a transmission-blocking single-chain antibody for expression in transgenic mosquitoes.

  PublisherOA PDFDOI

• A comprehensive Drosophila resource to identify key functional interactions between SARS-CoV-2 factors and host proteins

  Cell Reports · 2023-07-20 · 12 citations

  articleOpen accessSenior authorCorresponding

  Development of effective therapies against SARS-CoV-2 infections relies on mechanistic knowledge of virus-host interface. Abundant physical interactions between viral and host proteins have been identified, but few have been functionally characterized. Harnessing the power of fly genetics, we develop a comprehensive Drosophila COVID-19 resource (DCR) consisting of publicly available strains for conditional tissue-specific expression of all SARS-CoV-2 encoded proteins, UAS-human cDNA transgenic lines encoding established host-viral interacting factors, and GAL4 insertion lines disrupting fly homologs of SARS-CoV-2 human interacting proteins. We demonstrate the utility of the DCR to functionally assess SARS-CoV-2 genes and candidate human binding partners. We show that NSP8 engages in strong genetic interactions with several human candidates, most prominently with the ATE1 arginyltransferase to induce actin arginylation and cytoskeletal disorganization, and that two ATE1 inhibitors can reverse NSP8 phenotypes. The DCR enables parallel global-scale functional analysis of SARS-CoV-2 components in a prime genetic model system.

  PublisherOA PDFDOI

• Genetic conversion of a split-drive into a full-drive element

  Nature Communications · 2023-01-12 · 10 citations

  articleOpen accessSenior author

  The core components of CRISPR-based gene drives, Cas9 and guide RNA (gRNA), either can be linked within a self-contained single cassette (full gene-drive, fGD) or be provided in two separate elements (split gene-drive, sGD), the latter offering greater control options. We previously engineered split systems that could be converted genetically into autonomous full drives. Here, we examine such dual systems inserted at the spo11 locus that are recoded to restore gene function and thus organismic fertility. Despite minimal differences in transmission efficiency of the sGD or fGD drive elements in single generation crosses, the reconstituted spo11 fGD cassette surprisingly exhibits slower initial drive kinetics than the unlinked sGD element in multigenerational cage studies, but then eventually catches up to achieve a similar level of final introduction. These unexpected kinetic behaviors most likely reflect differing transient fitness costs associated with individuals co-inheriting Cas9 and gRNA transgenes during the drive process.

  PublisherOA PDFDOI

Recent grants

• NIH Grant R21AI060976

  NIH · $608k · 2007

• NIH Grant R01NS029870

  NIH · $5.3M · 2012

• Development of next-generation gene drive technologies for Anopheles population engineering

  NIH · $2.3M · 2021–2026

• NIH Grant R01GM060585

  NIH · $2.1M · 2007

• NIH Grant R56AI070654

  NIH · $364k · 2015

Frequent coauthors

• Bhagyashree Kaduskar

  Tata Institute for Genetics and Society

  28 shared

• John M. Marshall

  Innovative Genomics Institute

  24 shared

• Anthony A. James

  University of California, Irvine

  23 shared

• Valentino M. Gantz

  University of California, San Diego

  22 shared

• Annabel Guichard

  University of California, San Diego

  20 shared

• Arunachalam Ramaiah

  Milwaukee Health Department

  19 shared

• Yuh Nung Jan

  University of California, San Francisco

  17 shared

• Subhashini Srinivasan

  Institute of Bioinformatics and Applied Biotechnology

  16 shared