- Assistant Professor, Molecular and Cellular Biology
- Assistant Professor, Astronomy
- Assistant Professor, Lunar and Planetary Laboratory
- Assistant Professor, Planetary Sciences
- Assistant Professor, Genetics - GIDP
- Assistant Professor, BIO5 Institute
Professor Betül Kaçar is an astrobiologist exploring the origins of life on Earth and finding life on other planets in the Universe. She is an Assistant Professor at the University of Arizona in the Departments of Molecular & Cellular Biology as well as Astronomy and the Lunar & Planetary Laboratories. Prior to Arizona, she was a NASA Astrobiology Postdoctoral Fellow and a Research Leader at Harvard University where she developed molecular systems to bring ancient DNA sequences into the laboratory for physical, chemical and biological characterization. Her research is supported by NASA Exobiology and Evolutionary Biology Programs, NASA Astrobiology Program, the John Templeton Foundation, the National Science Foundation, Harvard University Origins Initiative as well as the University of Arizona Foundation.
Betul is one of the Principal Investigators of the NASA Astrobiology Institute Reliving the Past node, is an associate member of the NASA Nexus for Exoplanet System Science designed to foster interdisciplinary collaboration in the search for life on exoplanets, and currently holds an Adjunct Professor position at Earth-Life Science Institute in Tokyo, Japan, which is dedicated to understanding the origins of life. She was named a Scialog Fellow of the Heising-Simons Foundation and Kavli Foundation to study the Biosignatures and Life in the Universe in 2020, a NASA Early Career Fellow in 2019, and a Way Cool Scientist by the Science Club for Girls in 2017. Her research has gained national and international attention, and has been featured by CNN, BBC, NOVA Science, Discover Magazine, NPR Science Friday and Scientific American.
- Scialog Fellowship
- Heising-Simons FoundationResearch Corporation for Science Advancement, Winter 2020
- NASA Early Career Fellowship
- NASA, Fall 2019
- Way Cool Scientist
- Science Club for Girls, Spring 2017
astrobiology, molecular biology, evolution
astrobiology, molecular evolution
Directed RsrchMCB 392 (Spring 2020)
Directed RsrchMCB 492 (Spring 2020)
Honors Independent StudyMCB 199H (Spring 2020)
Lab Present & DiscussMCB 496A (Spring 2020)
ResearchGENE 900 (Spring 2020)
ThesisMCB 910 (Spring 2020)
Directed RsrchMCB 392 (Fall 2019)
Directed RsrchMCB 492 (Fall 2019)
Honors Independent StudyMCB 199H (Fall 2019)
Honors Independent StudyMCB 299H (Fall 2019)
Independent StudyMCB 299 (Fall 2019)
Introduction to ResearchMCB 795A (Fall 2019)
Lab Present & DiscussMCB 496A (Fall 2019)
Lab Presentations & DiscussionMCB 696A (Fall 2019)
Scientific CommunicationMCB 575 (Fall 2019)
What is MCB?MCB 195I (Fall 2019)
Directed ResearchASTR 492 (Spring 2019)
Directed RsrchMCB 392 (Spring 2019)
Honors Independent StudyMCB 199H (Spring 2019)
Lab Present & DiscussMCB 496A (Spring 2019)
Directed ResearchASTR 492 (Fall 2018)
Honors Independent StudyMCB 199H (Fall 2018)
Lab Presentations & DiscussionMCB 696A (Fall 2018)
ResearchMCB 900 (Fall 2018)
Scientific CommunicationMCB 575 (Fall 2018)
Introduction to ResearchMCB 795A (Spring 2018)
- Garcia, A. K., McShea, H., Kolaczkowski, B., & Kaçar, B. (2020). Reconstructing the evolutionary history of nitrogenases: Evidence for ancestral molybdenum-cofactor utilization. Geobiology.More infoThe nitrogenase metalloenzyme family, essential for supplying fixed nitrogen to the biosphere, is one of life's key biogeochemical innovations. The three forms of nitrogenase differ in their metal dependence, each binding either a FeMo-, FeV-, or FeFe-cofactor where the reduction of dinitrogen takes place. The history of nitrogenase metal dependence has been of particular interest due to the possible implication that ancient marine metal availabilities have significantly constrained nitrogenase evolution over geologic time. Here, we reconstructed the evolutionary history of nitrogenases, and combined phylogenetic reconstruction, ancestral sequence inference, and structural homology modeling to evaluate the potential metal dependence of ancient nitrogenases. We find that active-site sequence features can reliably distinguish extant Mo-nitrogenases from V- and Fe-nitrogenases and that inferred ancestral sequences at the deepest nodes of the phylogeny suggest these ancient proteins most resemble modern Mo-nitrogenases. Taxa representing early-branching nitrogenase lineages lack one or more biosynthetic nifE and nifN genes that both contribute to the assembly of the FeMo-cofactor in studied organisms, suggesting that early Mo-nitrogenases may have utilized an alternate and/or simplified pathway for cofactor biosynthesis. Our results underscore the profound impacts that protein-level innovations likely had on shaping global biogeochemical cycles throughout the Precambrian, in contrast to organism-level innovations that characterize the Phanerozoic Eon.
- Liberles, D. A., Chang, B., Geiler-Samerotte, K., Goldman, A., Hey, J., Kaçar, B., Meyer, M., Murphy, W., Posada, D., & Storfer, A. (2020). Emerging Frontiers in the Study of Molecular Evolution. Journal of molecular evolution.More infoA collection of the editors of Journal of Molecular Evolution have gotten together to pose a set of key challenges and future directions for the field of molecular evolution. Topics include challenges and new directions in prebiotic chemistry and the RNA world, reconstruction of early cellular genomes and proteins, macromolecular and functional evolution, evolutionary cell biology, genome evolution, molecular evolutionary ecology, viral phylodynamics, theoretical population genomics, somatic cell molecular evolution, and directed evolution. While our effort is not meant to be exhaustive, it reflects research questions and problems in the field of molecular evolution that are exciting to our editors.
- Garcia, A. K., & Kaçar, B. (2019). How to resurrect ancestral proteins as proxies for ancient biogeochemistry. Free Radical Biology & Medicine, 140, 260-269.More infoThroughout the history of life, enzymes have served as the primary molecular mediators of biogeochemical cycles by catalyzing the metabolic pathways that interact with geochemical substrates. The byproducts of enzymatic activities have been preserved as chemical and isotopic signatures in the geologic record. However, interpretations of these signatures are limited by the assumption that such enzymes have remained functionally conserved over billions of years of molecular evolution. By reconstructing ancient genetic sequences in conjunction with laboratory enzyme resurrection, preserved biogeochemical signatures can instead be related to experimentally constrained, ancestral enzymatic properties. We may thereby investigate instances within molecular evolutionary trajectories potentially tied to significant biogeochemical transitions evidenced in the geologic record. Here, we survey recent enzyme resurrection studies to provide a reasoned assessment of areas of success and common pitfalls relevant to ancient biogeochemical applications. We conclude by considering the Great Oxidation Event, which provides a constructive example of a significant biogeochemical transition that warrants investigation with ancestral enzyme resurrection. This event also serves to highlight the pitfalls of facile interpretation of paleophenotype models and data, as applied to two examples of enzymes that likely both influenced and were influenced by the rise of atmospheric oxygen - RuBisCO and nitrogenase.
- Adam, Z. R., Fahrenbach, A., Kacar, B., & Aono, M. (2018). Prebiotic Geochemical Automata At The Intersection Of Radiolytic Chemistry, Physical Complexity And Systems Biology. Complexity.
- Kacar, B. (2018). Exoplanet Biosignatures: Future Directions. Astrobiology.More infoExoplanet science promises a continued rapid accumulation of new observationsin the near future, energizing a drive to understand and interpret theforthcoming wealth of data to identify signs of life beyond our Solar System.The large statistics of exoplanet samples, combined with the ambiguity of ourunderstanding of universal properties of life and its signatures, necessitate aquantitative framework for biosignature assessment Here, we introduce aBayesian framework for guiding future directions in life detection, whichpermits the possibility of generalizing our search strategy beyondbiosignatures of known life. The Bayesian methodology provides a language todefine quantitatively the conditional probabilities and confidence levels offuture life detection and, importantly, may constrain the prior probability oflife with or without positive detection. We describe empirical and theoreticalwork necessary to place constraints on the relevant likelihoods, includingthose emerging from stellar and planetary context, the contingencies ofevolutionary history and the universalities of physics and chemistry. Wediscuss how the Bayesian framework can guide our search strategies, includingdetermining observational wavelengths or deciding between targeted searches orlarger, lower resolution surveys. Our goal is to provide a quantitativeframework not entrained to specific definitions of life or its signatures,which integrates the diverse disciplinary perspectives necessary to confidentlydetect alien life.[Journal_ref: ]
- Kacar, B., & Womack, Y. (2018). Future Shaped By Pasts That Could Have Been. Journal of Design and Science.
- Walker, S. I., Bains, W., Cronin, L., DasSarma, S., Danielache, S., Domagal-Goldman, S., Kacar, B., Kiang, N. Y., Lenardic, A., Reinhard, C. T., Moore, W., Schwieterman, E. W., Shkolnik, E. L., & Smith, H. B. (2018). Exoplanet Biosignatures: Future Directions. Astrobiology, 18(6), 779-824.More infoWe introduce a Bayesian method for guiding future directions for detection of life on exoplanets. We describe empirical and theoretical work necessary to place constraints on the relevant likelihoods, including those emerging from better understanding stellar environment, planetary climate and geophysics, geochemical cycling, the universalities of physics and chemistry, the contingencies of evolutionary history, the properties of life as an emergent complex system, and the mechanisms driving the emergence of life. We provide examples for how the Bayesian formalism could guide future search strategies, including determining observations to prioritize or deciding between targeted searches or larger lower resolution surveys to generate ensemble statistics and address how a Bayesian methodology could constrain the prior probability of life with or without a positive detection. Key Words: Exoplanets-Biosignatures-Life detection-Bayesian analysis. Astrobiology 18, 779-824.
- Kacar, B., Garmendia, E., Tuncbag, N., Andersson, D. I., & Hughes, D. (2017). Functional Constraints on Replacing an Essential Gene with Its Ancient and Modern Homologs. mBio, 8(4).More infoGenes encoding proteins that carry out essential informational tasks in the cell, in particular where multiple interaction partners are involved, are less likely to be transferable to a foreign organism. Here, we investigated the constraints on transfer of a gene encoding a highly conserved informational protein, translation elongation factor Tu (EF-Tu), by systematically replacing the endogenous tufA gene in the Escherichia coli genome with its extant and ancestral homologs. The extant homologs represented tuf variants from both near and distant homologous organisms. The ancestral homologs represented phylogenetically resurrected tuf sequences dating from 0.7 to 3.6 billion years ago (bya). Our results demonstrate that all of the foreign tuf genes are transferable to the E. coli genome, provided that an additional copy of the EF-Tu gene, tufB, remains present in the E. coli genome. However, when the tufB gene was removed, only the variants obtained from the gammaproteobacterial family (extant and ancestral) supported growth which demonstrates the limited functional interchangeability of E. coli tuf with its homologs. Relative bacterial fitness correlated with the evolutionary distance of the extant tuf homologs inserted into the E. coli genome. This reduced fitness was associated with reduced levels of EF-Tu and reduced rates of protein synthesis. Increasing the expression of tuf partially ameliorated these fitness costs. In summary, our analysis suggests that the functional conservation of protein activity, the amount of protein expressed, and its network connectivity act to constrain the successful transfer of this essential gene into foreign bacteria.IMPORTANCE Horizontal gene transfer (HGT) is a fundamental driving force in bacterial evolution. However, whether essential genes can be acquired by HGT and whether they can be acquired from distant organisms are very poorly understood. By systematically replacing tuf with ancestral homologs and homologs from distantly related organisms, we investigated the constraints on HGT of a highly conserved gene with multiple interaction partners. The ancestral homologs represented phylogenetically resurrected tuf sequences dating from 0.7 to 3.6 bya. Only variants obtained from the gammaproteobacterial family (extant and ancestral) supported growth, demonstrating the limited functional interchangeability of E. coli tuf with its homologs. Our analysis suggests that the functional conservation of protein activity, the amount of protein expressed, and its network connectivity act to constrain the successful transfer of this essential gene into foreign bacteria.
- Kacar, B., Guy, L., Smith, E., & Baross, J. (2017). Resurrecting ancestral genes in bacteria to interpret ancient biosignatures. Philosophical transactions. Series A, Mathematical, physical, and engineering sciences, 375(2109).More infoTwo datasets, the geologic record and the genetic content of extant organisms, provide complementary insights into the history of how key molecular components have shaped or driven global environmental and macroevolutionary trends. Changes in global physico-chemical modes over time are thought to be a consistent feature of this relationship between Earth and life, as life is thought to have been optimizing protein functions for the entirety of its approximately 3.8 billion years of history on the Earth. Organismal survival depends on how well critical genetic and metabolic components can adapt to their environments, reflecting an ability to optimize efficiently to changing conditions. The geologic record provides an array of biologically independent indicators of macroscale atmospheric and oceanic composition, but provides little in the way of the exact behaviour of the molecular components that influenced the compositions of these reservoirs. By reconstructing sequences of proteins that might have been present in ancient organisms, we can downselect to a subset of possible sequences that may have been optimized to these ancient environmental conditions. How can one use modern life to reconstruct ancestral behaviours? Configurations of ancient sequences can be inferred from the diversity of extant sequences, and then resurrected in the laboratory to ascertain their biochemical attributes. One way to augment sequence-based, single-gene methods to obtain a richer and more reliable picture of the deep past, is to resurrect inferred ancestral protein sequences in living organisms, where their phenotypes can be exposed in a complex molecular-systems context, and then to link consequences of those phenotypes to biosignatures that were preserved in the independent historical repository of the geological record. As a first step beyond single-molecule reconstruction to the study of functional molecular systems, we present here the ancestral sequence reconstruction of the beta-carbonic anhydrase protein. We assess how carbonic anhydrase proteins meet our selection criteria for reconstructing ancient biosignatures in the laboratory, which we term palaeophenotype reconstruction.This article is part of the themed issue 'Reconceptualizing the origins of life'.
- Kacar, B. (2020, 02). Reconstructed Enzymes as Proxies for Ancient Biophysical Processes (Plenary Talk). Biophysical Society Annual Meeting. San Diego, CA: Biophysical Society.
- Kacar, B. (2019, 03). Stepping into the past: Exploring the limits of biological resurrection. ASU BEYOND Coffee Seminars. Arizona State University: ASU.
- Kacar, B. (2019, 04). Recapitulating ancient history in the laboratory with the methods of evolutionary synthetic biology. Annual Rocky Mountain Geobiology Symposium (Keynote). Boulder, CO.
- Kacar, B. (2019, 05). Mechanisms driving evolutionary innovations. Evolution of Complex Life (Plenary Lecture). Georgia Tech: Georgia Tech College of Science.
- Kacar, B. (2019, 07). Reconstructed Enzymes as Proxies for Ancient Biogeochemical Intermediaries. Gordon Research Conference - Applied and Environmental Microbiology (Keynote Lecture). Holyoke, MA: Gordon Research Conferences.
- Kacar, B. (2019, 08). Stepping into the Past: Recreating Ancient Biology in the Laboratory. LPL Colloquium. UArizona: LPL.
- Kacar, B. (2019, 09). Probing the malleability of the bacterial translation machinery. Harvard Origins Seminar. Cambridge, MA: Harvard.
- Kacar, B. (2019, 10). Evolving a broken translation machinery to understand historical malleability. UNC Departmental Seminar. Chapel Hill: UNC Biology Department.
- Kacar, B. (2019, October). Breaking (not so) bad: Evolving a broken translation machinery to understand historical malleability. MCB Seminar. UA: MCB - Ross Buchan.
- Venkataram, S., & Kacar, B. (2019, 07). Seek and Destroy: Laboratory Evolution of Bacteria with a Disrupted Translation Machinery. Gordon Research Conference - Microbial Population Biology. NH: Gordon Research Conferences.More infoPostdoc presented my work due to my limited travel (sick child)
- Zhang, X., Kacar, B., & Kopf, S. (2019, 08). Understanding the Biogeochemistry of Nitrogen Inputs and Outputs from Molecular to Global Scales. American Geological Union.
- Garcia, A. K., McShea, H., Kolaczkowski, B., & Kacar, B. (2019, 10). Inferring the evolutionary history of nitrogenase metal utilization. Geological Society of America.
- Garcia, A., McShea, H., Kolaczkowski, B., & Kacar, B. (2019, 07). Reconstruction of ancestral nitrogenases: phylogenetic and structural implications for metal binding. Astrobiology Science Conference. Seattle, WA: NASA.
- Kacar, B. (2019, 07). Biophysical constraints on Precambrian Rubisco Evolution. Astrobiology Science Conference. Seattle, WA: NASA.
- Kacar, B., Battistuzzi,, F., Garcia, A., & Hedges, B. (2019, 07). Evolution of life’s complexity on a habitable planet. Astrobiology Science Conference. Seattle, WA.
- Sephus, C., & Kacar, B. (2019, 09). Shedding light on phototrophic pigment evolution: Reconstruction of ancestral rhodopsins. Geological Society of America. Phoenix, AZ.