About

Catherine Liu is a Professor of Film & Media Studies at UC Irvine, with a Ph.D. from the Graduate Center, CUNY, obtained in 1994. Her research interests include the intellectual history of class versus identity problems in an age of inequality, political economy of populism, Sinophone cinema, and critiques of the Professional Managerial Class. She works on Critical Theory of the traditional kind and engages in a long-term critique of liberal politics driven by the Professional Managerial Class. Liu is the author of 'Virtue Hoarders: The Case Against the Professional Managerial Class' published in 2021 and 'The American Idyll: Academic Anti-Elitism as Cultural Critique' published in 2011. Her work also explores the history of film genres, identity politics, populism, and the workings of the Professional Managerial Class, with a focus on cultural critique and political economy. She has held various academic positions, including associate professorship at the University of Minnesota and visiting roles at Bard College, Queensland University of Technology, and Tainan National University of the Arts. Liu has contributed to numerous publications and has been recognized through grants such as the Mellon-Pew Post-doctoral Fellowship and Fulbright Teaching Fellowships.

Research topics

• Biology
• Genetics
• Computer Science
• Computational biology
• Biochemistry
• Chemistry
• Cell biology
• Artificial Intelligence
• Algorithm

Selected publications

• Continuous hypermutation and evolution of noncanonical amino acid synthases

  bioRxiv (Cold Spring Harbor Laboratory) · 2026-03-12

  articleOpen accessSenior authorCorresponding

  Abstract Genetic code expansion (GCE) enables the site-specific incorporation of noncanonical amino acids (ncAAs) into proteins but is constrained by reliance on exogenously supplied chiral ncAAs. Achieving intracellular ncAA biosynthesis would enable more scalable and cost-effective GCE. Here, we report the continuous hypermutation and evolution of amino acid synthases that produce high levels of ncAAs inside yeast, thus supporting GCE from simple ncAA precursors. We encoded an engineered ‘tyrosine synthase’ ( Tm TyrS) on an error-prone orthogonal DNA replication system (OrthoRep) and selected variants based on ncAA biosynthesis from readily available phenol analogs and intracellular L-serine. Our selection employed orthogonal ncAA-specific aminoacyl-tRNA synthetases (aaRSs) as biosensors whereby target ncAA production leads to aminoacylation of an amber suppressor tRNA and the translation of a selectable reporter containing an amber stop codon. Our evolution successfully yielded Tm TyrS variants that efficiently produced 3-iodo-, 3-bromo-, 3-chloro-, and 3-methyl-L-tyrosine, enabling amber codon-specified ncAA-dependent translation, in some cases at levels comparable to sense codon-specified natural amino acid translation. This work reduces barriers for expressing proteins containing substituted tyrosines. Moreover, because aaRSs can themselves be evolved (including with OrthoRep) for a flexible range of ncAA specificities, these results establish an end-to-end framework for evolving ncAA biosynthetic enzymes in vivo . Graphical abstract We describe an OrthoRep-driven platform for evolving noncanonical amino acid (ncAA) synthases. Hypermutation of ncAA synthase genes enables evolution of ncAA biosynthesis from simple precursors, while intracellular ncAA production is linked to fluorescence via an orthogonal aaRS/tRNA system, allowing FACS enrichment of improved variants through iterative cycles.

  PublisherOA PDFDOI

• Biotin-Independent <i>Saccharomyces cerevisiae</i> with Enhanced Growth: Engineering an Acetyl-CoA Carboxylase Bypass

  ACS Synthetic Biology · 2025-06-03 · 5 citations

  article

  Throughout evolution, most Saccharomyces cerevisiae strains have lost their ability to synthesize biotin, an essential cofactor of several carboxylating enzymes. As a result, the essential vitamin or its precursors must be taken up from the environment and frequently supplemented in fermentations to achieve high cell densities. Engineering of a biotin-independent S. cerevisiae strain is of interest to eliminate the need for the external biotin supply. Herein, we describe the construction of a biotin-independent yeast strain by engineering a bypass of acetyl-CoA carboxylase, an essential biotin-dependent enzyme in the synthesis of fatty acids. Besides complete rescue of growth in biotin-free media, the resulting S. cerevisiae strains showed significantly improved growth on malonate compared to biotin. Beyond their industrial relevance, the yeast strains reported here can be valuable in areas of fundamental research, e.g., for developing a new selection marker or increasing the versatility of biotin–streptavidin technologies in living systems.

  PublisherDOI

• BoltzGen: Toward Universal Binder Design

  bioRxiv (Cold Spring Harbor Laboratory) · 2025-11-24 · 35 citations

  preprintOpen access

  , an all-atom generative model for designing proteins and peptides across all modalities to bind a wide range of biomolecular targets. BoltzGen builds strong structural reasoning capabilities about target-binder interactions into its generative design process. This is achieved by unifying design and structure prediction, resulting in a single model that also reaches state-of-the-art folding performance. BoltzGen's generation process can be controlled with a flexible design specification language over covalent bonds, structure constraints, binding sites, and more. We experimentally validate these capabilities in a total of eight diverse wetlab design campaigns with functional and affinity readouts across 26 targets. The experiments span binder modalities from nanobodies to disulfide-bonded peptides and include targets ranging from disordered proteins to small molecules. For instance, we test 15 nanobody and protein binder designs against each of nine novel targets with low similarity to any protein with a known bound structure. For both binder modalities, this yields nanomolar binders for 66% of targets. We release model weights, data, and both inference and training code at: https://github.com/HannesStark/boltzgen.

  PublisherOA PDFDOI

• Enterococcus and Eggerthella species are enriched in the gut microbiomes of COVID-19 cases in Uganda

  Gut Pathogens · 2025-02-04 · 2 citations

  articleOpen access

  BACKGROUND: Infection with the COVID-19-causing pathogen SARS-CoV-2 is associated with disruption in the human gut microbiome. The gut microbiome enables protection against diverse pathogens and exhibits dysbiosis during infectious and autoimmune disease. Studies based in the United States and China have found that severe COVID-19 cases have altered gut microbiome composition when compared to mild COVID-19 cases. We present the first study to investigate the gut microbiome composition of COVID-19 cases in a population from Sub-Saharan Africa. Given the impact of geography and cultural traditions on microbiome composition, it is important to investigate the microbiome globally and not draw broad conclusions from homogenous populations. RESULTS: We used stool samples in a Ugandan biobank collected from COVID-19 cases during 2020-2022. We profiled the gut microbiomes of 83 symptomatic individuals who tested positive for SARS-CoV-2 along with 43 household contacts who did not present any symptoms of COVID-19. The inclusion of healthy controls enables us to generate hypotheses about bacterial strains potentially related to susceptibility to COVID-19 disease, which is highly heterogeneous. Comparison of the COVID-19 patients and their household contacts revealed decreased alpha diversity and blooms of Enterococcus and Eggerthella in COVID-19 cases. CONCLUSIONS: Our study finds that the microbiome of COVID-19 individuals is more likely to be disrupted, as indicated by decreased diversity and increased pathobiont levels. This is either a consequence of the disease or may indicate that certain microbiome states increase susceptibility to COVID-19 disease. Our findings enable comparison with cohorts previously published in the Global North, as well as support new hypotheses about the interaction between the gut microbiome and SARS-CoV-2 infection.

  PublisherOA PDFDOI

• Ultra-efficient Integration of Gene Libraries onto Yeast Cytosolic Plasmids

  ACS Synthetic Biology · 2025-03-24 · 3 citations

  letterSenior authorCorresponding

  diversification of GOIs encoded on a cytosolic plasmid (p1), has been successfully used to drive numerous protein engineering campaigns. However, OrthoRep-based GOI evolution has almost always started from single GOI sequences, limiting the number of locations on a fitness landscape from where evolutionary search begins. Here, we present a simple approach for the high-efficiency integration of GOI libraries onto OrthoRep. By leveraging integrases, we demonstrate recombination of donor DNA onto the cytosolic p1 plasmid at exceptionally high transformation efficiencies, even surpassing the transformation efficiency of standard circular plasmids and linearized plasmid fragments into yeast. We demonstrate our method's utility through the straightforward construction of mock nanobody libraries encoded on OrthoRep, from which rare binders were reliably enriched. Overall, integrase-assisted manipulation of yeast cytosolic plasmids should enhance the versatility of OrthoRep in continuous evolution experiments and support the routine construction of large GOI libraries in yeast, in general.

  PublisherDOI

• Continuous Hypermutation and Evolution of Luciferase Variants

  ACS Chemical Biology · 2025-12-15 · 1 citations

  articleCorresponding

  Several luciferases have been developed for imaging and biosensing, and the collection continues to grow as new applications are pursued. The current workflow for luciferase optimization, while successful, remains laborious and inefficient. Mutant libraries are generated in vitro and screened, "winning" mutants are picked by hand, and the isolated sequences are subjected to additional rounds of mutagenesis and screening. Here, we present a streamlined platform for luciferase engineering that removes the need for manual library generation during each cycle. We purposed an orthogonal DNA replication (OrthoRep) system for continuous hypermutation of a well-known luciferase (GeNL). Short cycles of culturing and screening were sufficient to evolve the enzyme, with no repetitive manual library generation necessary. New GeNL variants were identified that exhibit improved light outputs with a noncognate and inexpensive luciferin. We further characterized the novel luciferases in cell models. Collectively this work establishes OrthoRep and continuous hypermutation as a viable method to engineer luciferases, and sets the stage for more rapid development of bioluminescent reporters.

  PublisherDOI

• Directed evolution of aminoacyl-tRNA synthetases through in vivo hypermutation

  Nature Communications · 2025-05-24 · 6 citations

  articleOpen accessSenior author

  Genetic code expansion (GCE) is a critical approach to the site-specific incorporation of non-canonical amino acids (ncAAs) into proteins. Central to GCE is the development of orthogonal aminoacyl-tRNA synthetase (aaRS)/tRNA pairs wherein engineered aaRSs recognize chosen ncAAs and charge them onto tRNAs that decode blank codons (e.g., the amber stop codon). However, evolving new aaRS/tRNA pairs traditionally relies on a labor-intensive process that often yields aaRSs with suboptimal ncAA incorporation efficiencies. Here, we present an OrthoRep-mediated strategy for aaRS evolution, which we demonstrate in 8 independent aaRS evolution campaigns, yielding multiple aaRSs that incorporate an overall range of 13 ncAAs tested. Some evolved systems enable ncAA-dependent translation at single amber codons with similar efficiency as natural translation at sense codons. Additionally, we discover an aaRS that regulated its own expression to enhance ncAA dependency. These findings demonstrate the potential of OrthoRep-driven aaRS evolution platforms to advance the field of GCE.

  PublisherOA PDFDOI

• The role of plasmid copy number and mutation rate in evolutionary outcomes

  Nature Ecology & Evolution · 2025-07-14 · 4 citations

  articleSenior author
  PublisherDOI

• Prediction of Single-Mutation Effects for Fluorescent Immunosensor Engineering with an End-to-End Trained Protein Language Model

  JACS Au · 2025-02-10

  articleOpen access

  A quenchbody (Q-body) is a fluorophore-labeled homogeneous immunosensor in which the fluorophore is quenched by tryptophan (Trp) residues in the vicinity of the antigen-binding paratope and dequenched in response to antigen binding. Developing Q-bodies against targets on demand remains challenging due to the large sequence space of the complementarity-determining regions (CDRs) related to antigen binding and fluorophore quenching. In this study, we pioneered a strategy using high-throughput screening and a protein language model (pLM) to predict the effects of mutations on fluorophore quenching with single amino acid resolution, thereby enhancing the performance of Q-bodies. We collected yeasts displaying nanobodies with high- and low-quenching properties for the TAMRA fluorophore from a modified large synthetic nanobody library followed by next-generation sequencing. The pretrained pLM, connected to a single-layer perceptron, was trained end-to-end on the enriched CDR sequences. The achieved quenching prediction model that focused on CDR1 + 3 performed best in the evaluation with precision-recall curves. Using this model, we predicted and validated the effective mutations in two anti-SARS-CoV-2 nanobodies, RBD1i13 and RBD10i14, which converted them into Q-bodies. For RBD1i13, three Trp mutants were predicted to have high probability scores for quenching through in silico Trp scanning. These mutants were verified via yeast surface display, and all showed enhanced quenching. For RBD10i14, mutations at four positions close to an existing Trp gave high scores through in silico saturation mutagenesis scanning. Six of eight high-score mutants, derived from two mutants at each of the four positions, exhibited deeper quenching on the yeast surface. Next, combined with the investigation of antigen binding of the mutants, we successfully achieved Q-bodies with enhanced responses. Overall, our strategy allows the prediction of fluorescence responses solely on the basis of the antibody sequence and will be essential for the rational selection and design of antibodies to achieve immunosensors with larger responses.

  PublisherDOI

• Mapping the evolution of computationally designed protein binders

  bioRxiv (Cold Spring Harbor Laboratory) · 2025-10-05 · 1 citations

  preprintOpen accessSenior authorCorresponding

  Computational protein design enables the generation of binders that target specific epitopes on proteins. However, current approaches often require substantial screening from which hits require further affinity maturation. Methods for experimentally improving designed proteins and exploring their sequence-affinity landscapes could therefore streamline the development of high-affinity binders and inform future design strategies. Here, we use OrthoRep, a system for continuous hypermutation in vivo, to drive the evolution of computationally designed mini protein binders ("minibinders") that target a mammalian receptor. Despite their small sizes (59-72 amino acids), we successfully affinity matured multiple minibinders through strong selection for improved binding and also sampled new regions of minibinder fitness landscapes through extensive neutral drift. One evolved minibinder variant was used to construct a combinatorially complete sequence-affinity map for its six affinity increasing mutations, which revealed nearly full additivity in their contributions to binding. Another minibinder was subjected to both deep mutational scanning and extensive evolution under weak selection, resulting in an evolutionarily diverged collection of binder sequences that revealed non-additive relationships among mutations. Our results highlight that the affinity of computationally designed binders can be rapidly increased through evolution and provide a scalable approach for the evolutionary exploration and subsequent mapping of sequence-affinity landscapes. We suggest that this work will complement protein binder design both as a reliable experimental optimization process and as a vehicle for generating new training data.

  PublisherOA PDFDOI

Recent grants

• A High-Throughput Continuous Evolution System for in vivo Biosensor Engineering

  NIH · $2.3M · 2015–2020

• ERA SynBio: Orthogonal Replication as the Platform for an Episome

  NSF · $580k · 2015–2020

• Synthetic genetic systems for rapid biomolecular evolution in vivo

  NIH · $2.4M · 2020–2026

• Making antibody generation rapid, scalable, and democratic through machine learning and continuous evolution

  NIH · $8.4M · 2020–2026

• A High-Throughput Continuous Evolution System for in vivo Biosensor Engineering

  NIH · $198k · 2015–2020

Frequent coauthors

• Benjamin Schwessinger

  Australian National University

  17 shared

• Anna Joe

  University of California, Davis

  16 shared

• Debora S. Marks

  Center for Systems Biology

  16 shared

• Pamela C. Ronald

  University of California, Berkeley

  16 shared

• Rory N. Pruitt

  16 shared

• Jay D. Keasling

  Joint BioEnergy Institute

  15 shared

• Christopher J. Petzold

  Joint BioEnergy Institute

  12 shared

• Leanne Jade G. Chan

  Lawrence Berkeley National Laboratory

  12 shared

Education

• Ph.D., French

  Graduate Center, CUNY

  1994

Awards & honors

• Mellon-Pew Post-doctoral Fellowship, California Institute of…
• McKnight Land Grant Professorship, University of Minnesota,…
• Queensland University of Technology Teaching Fellowship, Bri…
• Grant in Aid : University of Minnesota Graduate School (2004…
• Fulbright Teaching Fellowship to Tainan University of the Ar…