Introducing Our Authors - American Chemical Society

Mar 17, 2017 - Professor, Head of Molecular Engineering. Group, Institute for Molecular Bioscience and Australian .... application of the final synthe...
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Introducing Our Authors pubs.acs.org/synthbio



KIRILL ALEXANDROV

Education. B.S. in Molecular Biology, University of Graz, Austria; M.S. in Molecular Microbiology, University of Graz, Austria and at the Institute of Molecular Biology and Biotechnology (IMBB), Crete, Greece, Advisor: Nektarios Tavernarakis; Ph.D. in Biology, Molecular Microbial Physiology Group, University of Amsterdam, Advisor: Klaas Jan Hellingwerf; Postdoc, Systems Biology and Biological Physics Group, Institute of Science and Technology (IST) Austria, Klosterneuburg, Austria, Advisor: Tobias Bollenbach. Current Position. Postdoc (Marie Curie Fellow), Systems Biology and Biological Physics Group, Institute of Theoretical Physics, University of Cologne, Germany, Advisor: Tobias Bollenbach. Nonscientific Interests. Hiking, visiting museums (of all kinds), traveling, running, and climbing. In my Ph.D., I focused on metabolic engineering of cyanobacteria to produce commodities such as lactic acid or ethanol. To preserve a balance in the environment, I think that approaches based on biotechnology can provide a sustainable way for society to thrive on this planet. However, to reach this long-term goalthrough applied researchbasic research is indispensable to better understand nature. Studying microbes provides a great opportunity to understand life’s “design principles”. Microbes are an important entity on earth; they have colonized almost every environment and interact with virtually everything, from global (bio)chemical cycles to the health and disease states of higher organisms. In the lab, a reductionist approach helps us to disentangle the pathways that control growth of microbes. This is needed to understand how to counteract or support microbial growth in diverse environments. (Read Angermayr’s article DOI: 10.1021/acssynbio.6b00235).

Kirill Alexandrov.

Education. M.S. in Invertebrate Zoology Leningrad State University, U.S.S.R.; Ph.D. in Cell Biology, EMBL Heidelberg, Germany, Advisor: Dr. Marino Zerial. Current Position. Professor, Head of Molecular Engineering Group, Institute for Molecular Bioscience and Australian Institute for Bioengineering and Nanotechnology, Brisbane, Australia. Nonscientific Interests. Biotech entrepreneurship (cofounder of Jena Bioscience GmbH and Molecular Warehouse Ltd.), beer brewing, bread baking, cheese making, and swimming. We are interested in artificial sensing and two-way connectivity between biochemistry and electronics. Our group is developing a suite of technologies for rapid production of polypeptides with unnatural chemistries and properties and their use for construction of modular biological systems. We are very interested in the use of in vitro translation systems as rapid prototyping tools for protein and bioengineering. We developed a novel cell-free system based on Leishmania tarentolae and are now aiming to adapt it to production of complex polypeptides with unnatural amino acids using sense codon reassignment approach. (Read Alexandrov’s article DOI: 10.1021/acssynbio.6b00245).





FILIPE BRANCO DOS SANTOS

ANDREAS ANGERMAYR

Jos Arents.

Education. Ph.D. in microbiology and biotechnology at the Laboratory of Microbiology, Wageningen University, Advisor: Willem M. de Vos; Postdocs in systems biology at the Systems Received: March 2, 2017 Published: March 17, 2017

Bor Kavcic.

© 2017 American Chemical Society

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Introducing Our Authors

method was only applied to prokaryotic systems, we are now aiming to apply this method to eukaryotic systems and develop approaches for its scale up. (Read Cui’s article DOI: 10.1021/ acssynbio.6b00245).

Bioinformatics Group, Vrije University of Amsterdam, Advisor: Bas Teusink and at the Molecular Microbial Physiology Group, University of Amsterdam, Advisors: Klaas J. Hellingwerf and Jeroen Hugenholtz. Current Position. Assistant Professor of Molecular Microbiology at Swammerdam Institute for Life Sciences, University of Amsterdam. Nonscientific Interests. Reading, philosophy, music, traveling, and meeting people from different backgrounds. Microorganisms are often manipulated to be cell factories in biotechnological processes by genetic engineering alone. These strategies often neglect the effect on process stability that the added burden of product formation may present. Ultimately, this compromises their applicability in large-scale processes. Here, we focused on increasing production without further burdening the cells with increased expression of heterologous enzymes, by modulating allosteric effectors. We titrated the effect of their concentration on growth and production using a new 96-well based system developed for cyanobacteria. We observed that independent of expression levels, the fixation rate of spontaneous mutants harboring an impaired pathway is increased as carbon is deviated from growth to product. This is a challenge in cell factory development that may be offset by including inducible strategies such as the one pioneered here. (Read Branco dos Santos’s article DOI: 10.1021/acssynbio.6b00235).





WEI DU

Mengiing Sun.

Education. B.S. in Bioengineering, China Pharmaceutical University, China; M.S. in University of Chinese Academy of Sciences, China, Advisor: Dr. Xuefeng Lu. Current Position. Ph.D. Candidate, Molecular Microbial Physiology Group, University of Amsterdam, Advisor: Dr. Filipe Branco dos Santos. Nonscientific Interests. Mountain hiking, especially with ocean views, volleyball, and watching movies. My research focuses on cyanobacterial physiology, with the aim of development of stable cyanobacterial cell factories through directly converting CO2 into relevant chemical compounds. Cyanobacteria have been extensively genetically engineered recently for a variety of compounds production, yet only few of them stated briefly about the genetic instability issue. In short, this issue is due to microbial evolvability, where spontaneous mutations occurring in the introduced gene(s) for target compound production would be fixed because of enhanced cell growth fitness. In this contribution, we reported a different strategy (allosteric regulation) to boost L-lactic acid production. By means of this strategy, we clearly show that this instability is caused by deviating the fixed carbon from biomass formation, rather than by any other effect, such as protein burden. (Read Du’s article DOI: 10.1021/acssynbio.6b00235).

ZHENLING CUI

Xiang Liu.

Education. M.S. in Biochemistry and Molecular Biology in Qingdao Institute of Bioenergy and Bioprocess Technology, Chinese Academy of Science; Ph.D. in Chemical and Biological Sciences in Institute for Molecular Bioscience, The University of Queensland, Advisor: Prof. Kirill Alexandrov. Current Position. Research officer, Institute for Molecular Bioscience, Brisbane, Australia. Nonscientific Interests. Gym group training, tennis, swimming, and reading. My research interest lies in exploiting redundancy of the genetic code for site-selective unnatural amino acids (uAAs) incorporation into recombinant proteins produced in vitro. In our paper, we described a fractionation-based tRNA depletion method for preparing an Escherichia coli in vitro translation system lacking AGG-decoding tRNA isoacceptors. This system allows multisite-selective incorporation of uAAs by combining reassignment of sense (AGG) and nonsense codons. We successfully applied this approach to produce calmodulin protein harboring FRET-forming fluorescent probes. As the current



SHUICHI HOSHIKA

Kevin Bradley.

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Education. B.S.; M.S.; Ph.D. in Faculty Pharmaceutical Sciences, Hokkaido University (Japan), Advisor: Prof. Akira Matsuda. Current Position. Senior Scientist, Foundation for Applied Molecular Evolution. Alachua, FL. Nonscientific Interests. Puppies. I am interested in developing some tools and toys using unnatural nucleic acids. Especially, my research is focused on unnatural nucleic acids having unnatural nucleobases called as Artificial Expanded Genetic Information Systems (AEGIS) being developed at the Foundation for Applied Molecular Evolution in FL. With this system, I am trying to develop some functional DNA/RNA molecules, which some may work the same as natural nucleotides, some may work similar to natural nucleotides, or some may work different from natural nucleotides. I am also interested in constructing unnatural genetic system using AEGIS, which can create an artificial life. (Read Hoshika’s article DOI: 10.1021/acssynbio.6b00228).



Introducing Our Authors

MYONG-JUNG KIM

Kevin Bradley.

Education. B.S. in pharmacy, Seoul National University, Korea; M.S. and Ph.D. in medicinal chemistry, Seoul National University, Korea. Current Position. Research associate, Foundation for Applied Molecular Evolution, Alachua, FL. Nonscientific Interests. Traveling and watching sports. My current research involved the development of artificially expanded genetic information system (AEGIS) which increase the number of independently replicable nucleotides in DNA from 4 to 12 by rearranging hydrogen bond donor and acceptor groups on the nucleobases. (Read Kim’s article DOI: 10.1021/ acssynbio.6b00228).

NICOLAI KALLSCHEUER



CLAUDIA KNIELY

Nicolai Kallscheuer.

Education. B.Sc. Biotechnology and M.Sc. Biotechnology, both at Aachen University of Applied Sciences, Germany. Current Position. Ph.D. student at Forschungszentrum Juelich GmbH, Germany, Institute of Bio- and Geosciences (IBG-1), Research Group: Synthetic Cell Factories, Advisor: Prof. Michael Bott. Nonscientific Interests. Water polo, swimming, biking, and reading. My Ph.D. work focuses on metabolic engineering of the industrial workhorse Corynebacterium glutamicum toward the production of plant natural products, in particular of polyphenols showing pharmaceutically relevant properties. The engineered microbial production of polyphenols with C. glutamicum required not only the functional introduction of relevant heterologous pathways from plants, but also the abolishment of degradation pathways for aromatic compounds in the host. In addition, the central carbon metabolism had to be engineered toward overproduction of precursor metabolites. For production of the polyphenol resveratrol, a novel synthetic pathway was developed, which is based on the non-natural reversal of a microbial degradation pathway. In combination with plant enzymes, these pathways allowed resveratrol production from bulk chemicals in C. glutamicum. (Read Kallscheuer’s article DOI: 10.1021/acssynbio.6b00291).

Harald Alge.

Education. B.Sc. in Molecular Biology, Graz University of Technology and Karl-Franzens-University Graz University of Graz. Current Position. Master’s student of biotechnology, Graz University of Technology, Austria. Nonscientific Interests. Transforming taste combinations into delicious food, sports, and keeping my body in a strong condition. As a master’s student, I am able to perform experiments in various projects, allowing me to gain practical knowledge in the wide field of biotechnology. I appreciate being selected to support this project on core promoter design. I took part by investigating gene expression and other supporting tests to confirm the stability of the promoter’s strength thereby supporting the robustness of our data. Such work and results require additional knowledge and more detailed investigations in the field of synthetic biology. (Read Kniely’s article DOI: 10.1021/acssynbio.6b00178). 384

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Introducing Our Authors

QUANFENG LIANG

I am interested in targeted therapies to treat the hypoxic fraction of tumors which are often resistant to chemo- and radiotherapy. My research involves the development of bioprobes to study the causes and consequences of cellular hypoxia, and the targeting of small molecule therapeutics to reduce systematic toxicity. In this paper, we present a synthetic biology approach to targeting tumor hypoxia by the conditional expression of a genetically encoded cyclic peptide inhibitor of hypoxia inducible factor 1 (HIF-1) dimerization. The inhibitor sequence is integrated onto the chromosome of engineered cells, under a dual control conditional promoter. This approach eliminates the need for chemical synthesis of the inhibitor and allows spatial and temporal control of inhibitor expression, demonstrating wider application to introduce molecular modulators of cellular pathways in response to biological stimuli. I am now working on a collaborative projected funded by the MRC using bioreductive approaches to target tumor hypoxia. (Read Mistry’s article DOI: 10.1021/acssynbio.6b00219).

Quanfeng Liang.

Education. B.S. and M.S. in school of life science, Shandong University, Advisor: Prof. Zhenming Chi; Ph.D. in Chinese Academy of Agricultural Sciences, Advisor: Prof. Min Lin. Current Position. Associate Professor, State Key Laboratory of Microbial Technology, School of Life Science, Shandong University, Jinan, 250100, People’s Republic of China. Nonscientific Interests. Music and travel. My research focuses on design and construction of genetic circuit for dynamically controlling synthetic pathway, and employing these devices to produce biochemicals. In our paper, we designed an autoinduced AND gate that responds to both microbial communities and the cell physiological state. The application of the final synthetic device was demonstrated using the polyhydroxybutyrate (PHB) production system. The AND gate system increased PHB production by 1−2-fold in Escherichia coli. This synthetic logic gate is a tool for developing a general dynamic regulation system in metabolic engineering in response to complex signals, without using a specific sensor. (Read Liang’s article DOI: 10.1021/acssynbio.6b00177).





EWA MARIA MUSIOL-KROLL

Thomas Härtner.

Education. B.S. and M.S. in Microbiology/Biotechnology, University of Tübingen, Germany, Advisor: Prof. Wolfgang Wohlleben; Ph.D. in Microbiology/Biotechnology, University of Tü bingen, Germany, University of Tü bingen, Germany, Advisors: Prof. Wolfgang Wohlleben and Dr. Tilmann Weber; Postdoc at the Novo Nordisk Foundation Center for Biosustainability, Technical University of Denmark, Advisor: Prof. Sang Yup Lee/Dr. Tilmann Weber. Current Position. Postdoctoral Researcher, University Tuebingen, Interfaculty Institute of Microbiology and Infection Medicine Tuebingen (IMIT), Department of Microbiology/ Biotechnology. Nonscientific Interests. Running, traveling, sewing, baking cakes, and reading. My research focuses on the development of new tools for polyketide (PK) engineering. I am particularly fascinated by the discrete acyltransferase (AT) enzymes, their biochemistry, substrate specificity and interactions with their PK synthases. The acyltransferases are essential for PK production as they provide the building blocks for product biosynthesis. KirCII from the kirromycin pathway belongs to the best studied examples of discrete acyltransferases with unique substrate specificity. In our work, we used the tailored malonyl-CoA (Coenzyme A) synthetase for substrate activation and exploited the promiscuity of KirCII to the non-natural, nonmalonyl-CoA extender units, allylmalonyl- and propargylmalonyl-CoA to produce new kirromycins with allyl- and propargyl-side chains.

ISHNA MISTRY

Ishna Mistry.

Education. Master’s in Natural Sciences (University of Southampton, Southampton); Ph.D. in Chemical Biology (University of Southampton, Southampton), Advisor: Prof. Ali Tavassoli. Current Position. Postdoctoral Researcher, Department of Oncology, University of Oxford, Oxford, UK, Advisors: Dr. Ester Hammond and Prof. Stuart Conway. Nonscientific Interests. Playing netball, going to the theater, and baking. 385

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Introducing Our Authors

Propargyl-kirromycin was utilized for further derivatization using click chemistry. Our achievements are the result of an interdisciplinary teamwork, where we were able to demonstrate that the combination of a “bio-derivatization” approach and click chemistry methods enables the production of novel compounds. Thus, we propose the MatB/KirCII-ACP5 system as potential tool for PK engineering and product derivatization. (Read Musiol-Kroll’s article DOI: 10.1021/acssynbio.6b00341).



Education. B.Sc. in Molecular and Cell Biology, NOVA University of Lisbon, Portugal; M.Sc. in Biotechnology, NOVA University of Lisbon, Portugal, Advisor: Prof. Rui Oliveira; Ph.D. in Biosystems Engineering, NOVA University of Lisbon (MIT-Pt program), Portugal, Advisor: Prof. Rui Oliveira. Current Position. Postdoc, Systems Biology and Engineering Lab., LAQV/REQUIMTE, Department of Chemistry, Faculty of Science and Technology, NOVA University of Lisbon, Portugal. Nonscientific Interests. Reading, traveling, and playing soccer. It is still challenging to accurately reflect all relevant mechanisms for a given biological process in a mathematical (parametric) model. Likewise, it is unrealistic that, even with high throughput methods, enough high quality data can be generated to deduce design principles using statistical (nonparametric) models. Such design principles could be used, in synthetic biology, to design standardized biological parts or systems with increasing complexity. A promising alternative approach is to merge these methods in a hybrid semiparametric model that complements the available mechanistic knowledge with principles inferred from data. Our present paper represents a first step toward a benchmark of these strategies for synthetic biology, with the case study of developing de novo general synthetic core promoters for yeasts using a data driven approach. (Read Portela’s article DOI: 10.1021/ acssynbio.6b00178).

ERNST OBERORTNER



ANAM QUDRAT Education. Honors B.Sc., York University, Canada, Advisor: Jean-Paul Paluzzi. Current Position. Ph.D. Candidate, Institute of Biomaterials and Biomedical Engineering (IBBME), University of Toronto, Canada, Advisor: Kevin Truong. Nonscientific Interests. Landscape photography and the Arabic language. My research interest is to design protein chimeras that use a Ca2+ signal to rewire a wide range of extracellular stimuli to diverse Ca2+activated processes such as motility, for targeted drug therapeutics. In this proof-of-principle study, we created four different chimeras that generate a Ca2+ signal upon stimulation with various extracellular stimuli including rapamycin, EDTA and high/low extracellular free Ca2+. Next, we coupled these chimeras to Ca2+responsive proteins to effectively rewire dynamic cellular blebbing to increases in extracellular free Ca2+. While this work establishes the validity of our design strategy, we are currently working to rewire various inflammatory cytokines such as TNFa and MCSF to accomplish directed migration toward inflammatory diseased sites. (Read Qudrat’s article DOI: 10.1021/acssynbio.6b00310).

Ernst Oberortner.

Education. Undergraduate degree from Vienna University of Technology, Advisor: Schahram Dustdar; Ph.D. from Vienna University of Technology, Advisors: Schahram Dustdar, Uwe Zdun; Postdoc from Boston University, Advisor: Douglas Densmore. Current Position. Software Developer at DOE Joint Genome Institute (JGI), Lawrence Berkeley National Laboratories (LBNL). Nonscientific Interests. Rock climbing, running, hiking, and traveling. One primary objective of the DOE JGI is to service users (academic laboratories, nonprofits, commercial entities) with building physical DNA sequences in a cost- and time-efficient manner at the maximum success rate. One of my scientific interests lies in the (standardized) design specification of biological systems and the streamlined compilation process from a design specifications into synthesizable and functioning DNA sequences. BOOST contributes to both, namely ensuring that the resulting DNA sequences can be synthesized at low cost, fast turnaround times, and high success rates. (Read Oberortner’s article DOI: 10.1021/acssynbio.6b00200).





RUI MIGUEL CORREIA PORTELA

BRANDON RAZOOKY

Samer Naif.

David Filipe Correia Portela.

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Education. B.S. Pharmacological Chemistry, University of California, San Diego; M.S. Chemistry and Biochemistry, University of California, San Diego, Advisor: Dr. Leor S. Weinberger; Ph.D. Biophysics, University of California, San Francisco, Advisor: Dr. Leor S. Weinberger; Postdoctoral Associate, Oak Ridge National Laboratory, Advisor: Dr. Michael L. Simpson; Postdoctoral Fellow, The Rockefeller University, Advisor: Dr. Alexander Tarakhovsky. Current Position. Postdoctoral Associate, The Rockefeller University, Laboratory of Virology and Infectious Disease; Advisor Dr. Charles Rice. Nonscientific Interests. Hiking, scotch, and trying to predict what will happen on Game of Thrones. Typically, how organisms resolve conflicts for limited resources is studied in the context of intercellular competition. However, intracellular components can be limiting and intracellular competition may shape how cells spatially and temporally regulate signaling, metabolism, and gene-expression processes. This paper focuses on the latter, i.e., how to optimally produce gene-expression products in the presence of a limited resource pool? This work provides evidence that time-domain multiplexing (TDM), separating events in time rather than space, can robustly produce expression products despite limited resources. The utilization of a synthetic “cell” also provides the unique opportunity to precisely control the molecular components and allotment of resources, providing a powerful tool to understand cellular processes. (Read Razooky’s article DOI: 10.1021/ acssynbio.6b00189).



JEONG SANG YI

Hosung Yi.

Education. B.S. University of Massachusetts Amherst. Current Position. Ph.D. Candidate, Seoul National University, School of Chemical and Biological Engineering, Advisor: Prof. Kim, Byung-Gee. Nonscientific Interests. Photography, music, and guitar. My research interests are in primary and secondary metabolisms of E. coli and Streptomyces sp. Currently, Streptomyces species produce vast majority of secondary metabolites such as antibiotics and anticancer drugs. But such valuable compounds are produced in such small quantities due to limited numbers of gene modification strategies. In this paper, only a small glimpse of what could be done with next generation sequencing data sets was presented with constructions of gene expression systems in Streptomyces sp. I believe when they are combined with techniques such as CRISPR and MAGE, metabolic engineering for productions of natural compounds would have another big step forward. (Read Yi’s article DOI: 10.1021/acssynbio.6b00263). 387

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