About

Zhanar Abil is an Assistant Professor in the Department of Biology at the University of Florida. She earned her Ph.D. in Biochemistry from the University of Illinois at Urbana-Champaign in 2015, where she was mentored by Huimin Zhao. Her academic background also includes a Bachelor of Science in Biotechnology from Indiana University Bloomington, with undergraduate research mentored by Eric Knox. Her research interests focus on understanding the mechanisms of biological processes and building a unified theory of life, particularly through the lens of synthetic biology. She aims to generate an artificial living system or synthetic cell by constructing cell-free genetic circuits that operate in positive feedback loops, which she refers to as Autocatalytic Gene Circuits (ACGCs). Her long-term goal is to create synthetic life that mimics the cyclically catalytic nature of living organisms, studying these systems to understand their ability to synthesize biopolymers, evolve, and integrate into more complex genetic networks. She has held positions as a scientific consultant at Strand Therapeutics and as a postdoctoral fellow at Delft Technical University and the University of Texas at Austin. Her work emphasizes bottom-up synthetic biology and the potential to re-build living systems from non-living components.

Research topics

• Biology
• Artificial Intelligence
• Computational biology
• Computer Science
• Genetics
• Molecular biology
• Cell biology

Selected publications

• CADGE 2.0, Transcription-Translation-Coupled DNA Replication is Improved in a Chemically Modified Cell-Free System

  bioRxiv (Cold Spring Harbor Laboratory) · 2026-03-01 · 1 citations

  articleOpen accessSenior authorCorresponding

  Abstract In vitro directed evolution in synthetic microcompartments can generally support the evolution of genes with functions beyond affinity. The main challenge in the implementation of this strategy is the need to incorporate no more than a single DNA template molecule per microcompartment, thereby establishing a robust genotype-phenotype linkage, but which results in slow, inconsistent in vitro transcription and translation (IVTT) and poor DNA recovery after selection or screening. To address this challenge, we previously developed CADGE (Clonal Amplification-enhanceD Gene Expression) a strategy that allows the clonal amplification of linear gene-encoding DNA and coupled, in situ transcription-translation of the gene of interest. Here, we show that clonal amplification is highly sensitive to the cell-free system’s composition and that robust, highly efficient cell-free DNA amplification via the CADGE platform can be achieved by replacing standard vendor-supplied energy mixes with DNA replication-optimized, homemade counterparts.

  PublisherOA PDFDOI

• Building a Synthetic Cell Together

  Nature Communications · 2025-08-12 · 11 citations

  reviewOpen access

  Synthetic cells (SynCells) are artificial constructs designed to mimic cellular functions, offering insights into fundamental biology, as well as promising impact in the fields of medicine, biotechnology, and bioengineering. Achieving a functional SynCell from the bottom up, i.e. by assembling it from molecular components, requires a global collaboration to overcome the many challenges of engineering and assembling life-like modules while addressing biosafety, equity, and ethical concerns in order to guide responsible innovation. Here, we highlight major scientific hurdles, such as the integration of functional modules by ensuring compatibility across diverse synthetic subsystems, and we propose strategies to advance the field. Synthetic cells are artificial constructs designed to mimic cellular functions, offering insights into fundamental biology, as well as promising impact in the fields of medicine, biotechnology, and bioengineering. In this perspective, the authors highlight major scientific hurdles, such as the integration of functional modules by ensuring compatibility across diverse synthetic subsystems, and propose strategies to advance the field.

  PublisherOA PDFDOI

• Darwinian Evolution of Self-Replicating DNA in a Synthetic Protocell

  bioRxiv (Cold Spring Harbor Laboratory) · 2024-04-30

  preprintOpen access1st author

  ABSTRACT Replication, heredity, and evolution are characteristic of Life. We and others have postulated that the reconstruction of a synthetic living system in the laboratory will be contingent on the development of a genetic self-replicator capable of undergoing Darwinian evolution. Although DNA-based life dominates, the in vitro reconstitution of an evolving DNA self-replicator has remained challenging. We hereby emulate in liposome compartments the principles according to which life propagates information and evolves. Using two different experimental configurations supporting intermittent or semi-continuous evolution (i.e., with or without DNA extraction, PCR, and re-encapsulation), we demonstrate sustainable replication of a linear DNA template – encoding the DNA polymerase and terminal protein from the Phi29 bacteriophage – expressed in the ‘protein synthesis using recombinant elements’ (PURE) system. The self-replicator can survive across multiple rounds of replication-coupled transcription-translation reactions in liposomes and, within only ten evolution rounds, accumulates mutations conferring a selection advantage. Combined data from next-generation sequencing with reverse engineering of some of the enriched mutations reveal nontrivial and context-dependent effects of the introduced mutations. The present results are foundational to build up genetic complexity in an evolving synthetic cell, as well as to study evolutionary processes in a minimal cell-free system.

  PublisherOA PDFDOI

• Darwinian Evolution of Self-Replicating DNA in a Synthetic Protocell

  Nature Communications · 2024 · 42 citations

  1st authorCorresponding
  • Biology
  • Genetics
  • Computational biology

  Replication, heredity, and evolution are characteristic of Life. We and others have postulated that the reconstruction of a synthetic living system in the laboratory will be contingent on the development of a genetic self-replicator capable of undergoing Darwinian evolution. Although DNA-based life dominates, the in vitro reconstitution of an evolving DNA self-replicator has remained challenging. We hereby emulate in liposome compartments the principles according to which life propagates information and evolves. Using two different experimental configurations supporting intermittent or semi-continuous evolution (i.e., with or without DNA extraction, PCR, and re-encapsulation), we demonstrate sustainable replication of a linear DNA template - encoding the DNA polymerase and terminal protein from the Phi29 bacteriophage - expressed in the 'protein synthesis using recombinant elements' (PURE) system. The self-replicator can survive across multiple rounds of replication-coupled transcription-translation reactions in liposomes and, within only ten evolution rounds, accumulates mutations conferring a selection advantage. Combined data from next-generation sequencing with reverse engineering of some of the enriched mutations reveal nontrivial and context-dependent effects of the introduced mutations. The present results are foundational to build up genetic complexity in an evolving synthetic cell, as well as to study evolutionary processes in a minimal cell-free system.

  PublisherOA PDFDOI

• Integrating metabolism and evolution towards the realization of synthetic life

  Nature Reviews Bioengineering · 2024-12-09 · 9 citations

  article1st authorCorresponding
  PublisherDOI

• Clonal Amplification-Enhanced Gene Expression in Synthetic Vesicles

  ACS Synthetic Biology · 2023 · 15 citations

  1st authorCorresponding
  • Biology
  • Computational biology
  • Molecular biology

  In cell-free gene expression, low input DNA concentration severely limits the phenotypic output, which may impair in vitro protein evolution efforts. We address this challenge by developing CADGE, a strategy that is based on clonal isothermal amplification of a linear gene-encoding dsDNA template by the minimal Φ29 replication machinery and in situ transcription-translation. We demonstrate the utility of CADGE in bulk and in clonal liposome microcompartments to boost up the phenotypic output of soluble and membrane-associated proteins, as well as to facilitate the recovery of encapsulated DNA. Moreover, we report that CADGE enables the enrichment of a DNA variant from a mock gene library via either a positive feedback loop-based selection or high-throughput screening. This new biological tool can be implemented for cell-free protein engineering and the construction of a synthetic cell.

  PublisherDOI

• Clonal amplification-enhanced gene expression for cell-free directed evolution

  bioRxiv (Cold Spring Harbor Laboratory) · 2022-11-17 · 1 citations

  preprintOpen access1st author

  Abstract In cell-free gene expression, low input DNA concentration severely limits the phenotypic output, which may impair in vitro protein evolution efforts. We address this challenge by developing CADGE, a strategy that is based on clonal isothermal amplification of a linear gene-encoding dsDNA template by the minimal Φ29 replication machinery and in situ transcription-translation. We demonstrate the utility of CADGE in bulk and in clonal liposome microcompartments to boost up the phenotypic output of soluble and membrane-associated proteins, as well as to facilitate the recovery of encapsulated DNA. Moreover, we report that CADGE enables the enrichment of a DNA variant from a mock gene library either via a positive feedback loop-based selection or high-throughput screening. This new biological tool can be implemented for cell-free protein engineering and the construction of a synthetic cell.

  PublisherOA PDFDOI

• Roadmap to Building a Cell: An Evolutionary Approach

  Frontiers in Bioengineering and Biotechnology · 2020 · 73 citations

  1st authorCorresponding
  • Computer Science
  • Computer Science
  • Artificial Intelligence

  definition of life. To achieve this goal, we propose in this perspective to undertake a semi-rational, system's level evolutionary approach. The strategy would require iterative cycles of genetic integration of functional modules, diversification of hereditary information, compartmentalized gene expression, selection/screening, and possibly, assistance from open-ended evolution. We explore the underlying challenges to each of these steps and discuss possible solutions toward the bottom-up construction of an artificial living cell.

  PublisherOA PDFDOI

• Divalent cations promote TALE DNA-binding specificity

  Nucleic Acids Research · 2019-12-06 · 12 citations

  articleOpen access

  Recent advances in gene editing have been enabled by programmable nucleases such as transcription activator-like effector nucleases (TALENs) and CRISPR-Cas9. However, several open questions remain regarding the molecular machinery in these systems, including fundamental search and binding behavior as well as role of off-target binding and specificity. In order to achieve efficient and specific cleavage at target sites, a high degree of target site discrimination must be demonstrated for gene editing applications. In this work, we studied the binding affinity and specificity for a series of TALE proteins under a variety of solution conditions using in vitro fluorescence methods and molecular dynamics (MD) simulations. Remarkably, we identified that TALEs demonstrate high sequence specificity only upon addition of small amounts of certain divalent cations (Mg2+, Ca2+). However, under purely monovalent salt conditions (K+, Na+), TALEs bind to specific and non-specific DNA with nearly equal affinity. Divalent cations preferentially bind to DNA over monovalent cations, which attenuates non-specific interactions between TALEs and DNA and further stabilizes specific interactions. Overall, these results uncover new mechanistic insights into the binding action of TALEs and further provide potential avenues for engineering and application of TALE- or TALEN-based systems for genome editing and regulation.

  PublisherOA PDFDOI

• Compartmentalized Self‐Replication for Evolution of a DNA Polymerase

  Current Protocols in Chemical Biology · 2018-03-01 · 9 citations

  article1st authorCorresponding

  Compartmentalized self-replication (CSR) is an emulsion PCR-based method for the selection of DNA polymerases. E. coli host cells expressing a library of DNA polymerases are emulsified so that no more than a single cell is present in a single emulsion droplet. In a subsequent emulsion PCR step, the DNA polymerase protein, as well as the plasmid encoding it are released into the emulsion droplet and the genes that created the most active or abundant polymerase variants are exponentially amplified and can be passed to the next round of CSR. CSR is a powerful method for engineering of polymerases since it allows selection under a variety of conditions, including the use of non-standard substrates. In this unit, we provide a step-by-step procedure for the selection of polymerases, using as an example the selection of reverse transcriptase activity starting from a library of Thermococcus kodakaraensis (KOD) DNA polymerase variants. © 2018 by John Wiley & Sons, Inc.

  PublisherDOI

Frequent coauthors

• Huimin Zhao

  19 shared

• Christophe Danelon

  Delft University of Technology

  11 shared

• Charles M. Schroeder

  Nathan Kline Institute for Psychiatric Research

  6 shared

• Luke Cuculis

  Urbana University

  5 shared

• Ana María Restrepo Sierra

  Delft University of Technology

  4 shared

• Yannick Rondelez

  ESPCI Paris

  3 shared

• Casper C. Hoogenraad

  3 shared

• Diwakar Shukla

  University of Illinois Urbana-Champaign

  3 shared

Labs

• The Abil LabPI