The Difference Between the Modern Gene Editing Tools ZFNs, TALENs, and CRISPR/Cas9, Restriction nuclease Fok1 fused to multiple zinc finger peptides, each target triplet codon of genomic DNA, Nonspecific DNA nuclease fused to a domain specific for a genomic loci, Repetitive sequence may cause unintended cuts to the DNA sequence, 20 nucleotide crRNA fused to Cas9 nuclease and tracrRNA, Highly specific and easy multiplexed gene editing, No limitation in high-throughput targeting. A Cas-ON switch for cell type-specific genome editing. With the advancements in new technologies and tools, the future of synthetic biology appears highly promising for sustainable development by providing solutions to the environmental pollution, bio-waste utilization, and commercial products development. demonstrated a modular genetic strategy for the design of bioinspired hybrid nanofibers by combining mussel foot proteins (Mfps) of Mytilus galloprovincialis with CsgA proteins (the major subunit of E. coli amyloid curli fibers) [11]. Until today, it has not been possible to build a living cell from single functional units, which may be attributed to the enormous complexity of molecules and modules in all known biological systems. These hybrid nanofibers were synthesized by protein expression and refolding and, more importantly, could hierarchically self-assemble into higher-order structures that exhibit strong adhesiveness, as illustrated in Figure 4.3. A large number of new biological circuits have been designed and successfully implemented in the past [9,38,40,43,47,122]. Biological parts include genes and regulatory sequences that can be tuned to optimize system behavior. This bottom-up strategy is commonly used in all of the fields of engineering, but is feasible only in a modular framework, where designers can predict the behavior of the composite system from the knowledge of basic parts functioning. In both predicted structures, CsgA forms the amyloid core, with Mfp3 and Mfp5 extending from CsgA’s C-terminal or N-terminal, respectively, as unstructured coil structures. Multidisciplinary Synthetic Biology Research Centres (SBRCs) Six SBRCs, representing a total investment of £70.5M , have been allocated funding over five years to boost national synthetic biology research capacity and ensure that there is diverse expertise to stimulate innovation in this area. 9.6 shows the tools, molecules, devices, and systems produced by synthetic biology that are important in diagnosis and therapeutics. Dominik obtained a M.Sc. Although the field of synthetic biology is still young, its proponents expect it to lead us to an exciting new era in biotechnology. Figure 1.1. The goal of synthetic biology is to make the construction of novel biological systems into a practical and useful engineering discipline. Furthermore, protein engineering has contributed to the production of chimeric proteins generating multivalent vaccines that are safer and more efficient [114,123,124]. The headline and subheader tells us what you're offering, and the form header closes the deal. While synthetic biology has demonstrated its potential to solve high-impact problems, a plethora of basic research studies are still ongoing to discover the engineering limits for biological systems. Nucleic Acids Research, 47(13), doi:10.1093/nar/gkz271, Upmeier zu Belzen, J., Bürgel, T., Holderbach, S., Bubeck, F., Adam, L., Gandor, C., Klein, M., Mathony, J., Pfuderer, P. L., Platz, L., Przybilla, M., Schwendemann, M., Heid, D., Hoffmann, M. D., Jendrusch, M., Schmelas, C., Waldhauer, M., Lehmann, I., Niopek, D.§ & Eils, R.§ (2019). Research Synthetic Biology. Table 9.1. In this chapter we have discussed the principles, methods of synthetic biology, and tools that can be applied to engineer various stages of central dogma keeping plant synthetic biology in perspective. (b) The modular design of artificial adhesive materials is enabled by rationally fusing genes encoding the two natural adhesive elements shown in (a). Enhanced underwater adhesion is expected to arise from the synergy between the high fiber surface area of curli and the adhesive residues from the Mfp domains. Anti-CRISPR proteins are potent inhibitors of CRISPR effectors. Synthetic biology has given a new dimension to biological aspects of science, and the collaboration of various streams such as engineering, mathematics, physics, and chemistry has led to the evolution of this highly fruitful field. Synthetic biology is the design and construction of new biological entities such as enzymes, genetic circuits, and cells or the redesign of existing biological systems. Due to its high autolytic activities, the pancreas is a very challenging, Professor Dominik Niopek, Department of Biology at the TU, has been awarded the "Life Sciences Bridge - Aventis Foundation Postdoctoral Award" research prize sponsored by the Aventis Foundation. Synthetic metabolic pathways have been constructed in Synechococcus elongatus PCC 7942 using genes from a range of other microorganisms. Synthetic biology is at its preliminary stage as a scientific field and needs time to mature up. They are typically delivered as seminars at university campuses or invited talks scientific conferences. In vitro copolymerization of the CsgA–Mfp3 and Mfp5–CsgA monomers can lead to hierarchically coassembled structures with two different adhesive domains displayed on amyloid scaffolds, potentially recapitulating intermolecular interactions between Mfp3 and Mfp5 molecules in natural mussel adhesion systems. Synthetic Biology is an online only open access journal publishing high quality, original peer-reviewed research on synthetic biology, including papers on the mathematical modelling and practical engineering in the field … Find out more While CASANOVA was initially limited to the S. pyogenes Cas9, we are currently extending this original strategy to other Cas9 orthologues and Cas12. Synthetic biology intends to reconstruct novel artificial biological systems, which can maintain the integrative complexity of central dogma in a rational and translational manner for the efficient production of desired biomolecules beneficial to the society. Leveraging implicit knowledge in neural networks for functional dissection and engineering of proteins. Towards this goal, we closely collaborate with Prof. Dr. Dirk Grimm at Heidelberg University clinics. Metabolomic tools such as HPLC, UPLC, LC-MS, GC-MS, MALDI-TOF, MS-TOF, and LC-NMR have been useful for qualitative and quantitative analysis of individual metabolite [42]. brings together two independent sites of excellent. Yet although it is a rapidly emerging field, it must be stressed that work on synthetic biology is still at a There has been long time that synthetic biology was tinkered with the idea of creating “made to order” microbes from well-characterized biological parts. A more detailed definition of synthetic biology. 1). Figure 4.3. We are pleased to present our recent achievements in building the Human Cell Atlas of the Pancreas on single-cell resolution. BCC Research examines the synthetic biology industry by market segment, including DNA sequencing, DNA synthesis, gene editing, synthetic biology foundries and software; as well as the agriculture; consumer products, cosmetics and skin care, food and beverage, healthcare and industrial chemicals enable product sectors. Nature Machine Intelligence 1, 225-235. doi: 10.1038/s42256-019-0049-9, Bubeck, F., Hoffmann, M. D., Harteveld, Z., Aschenbrenner, S., Bietz, A., Waldhauer, M. C., Börner, K., Fakhiri, J., Schmelas, C., Dietz, L., Grimm, D., Correia, B. E., Eils, R.§ & Niopek, D.§ (2018). Synthetic biology is a combination of biology and different branches of engineering, such as electrical, mathematical, mechanical, and computer, providing a greater ability of understanding and manipulation of the biological systems or creation of novel life forms [1]. by coupling Cas9 activity to the abundance of cell type-specific microRNAs (Hoffmann et al., 2019). ScienceDirect ® is a registered trademark of Elsevier B.V. ScienceDirect ® is a registered trademark of Elsevier B.V. Genome Engineering Tools in Plant Synthetic Biology, Current Developments in Biotechnology and Bioengineering, Biosynthetic Technology and Bioprocess Engineering, Biosynthesis of High-Value Amino Acids by Synthetic Biology, Applications and Future Perspectives of Synthetic Biology Systems, Synthetic Metabolism and Its Significance in Agriculture, Bioinspired nanopolymers and nanocomposites for orthopedic applications, Nanotechnology-Enhanced Orthopedic Materials, Synthetic biology of cyanobacteria for production of biofuels and high-value products, Microalgae-Based Biofuels and Bioproducts, Modelling Methodology for Physiology and Medicine (Second Edition), Systems and Synthetic Biology Applied to Health, Current Opinion in Biomedical Engineering. Synthetic biology is considered as an emerging research field that will bring new opportunities to biotechnology. (d) Because of the amyloidogenic domains, CsgA–Mfp3 and Mfp5–CsgA monomers can self-assemble into large bundles of fibrils or hierarchical networks of filaments. Over here you can explain why your offer is so great it's worth filling out a form for. The, We are pleased to announce our novel computational model for reducing off-target effects in CRISPR-Cas9 approaches: The manuscript Coupling Cas9 to artificial inhibitory domains enhances CRISPR-Cas9. in Molecular Biotechnology at Heidelberg University. From: Microbial Electrochemical and Fuel Cells, 2016, Krishan Mohan Rai, ... Venugopal Mendu, in Current Developments in Biotechnology and Bioengineering, 2019. Light-activated binding of SpydCas9-RFP to telomeres. HIDIH’s major branch in Berlin is the Center for Digital Health at the Charité and the Berlin Institute of Health (BIH). CRISPR, clustered regularly interspaced short palindromic repeats; TALENs, transcription activator-like effector nucleases; ZFNs, zinc-finger nucleases. Harnessing AI & machine learning to rationalise and accelerate the computational design of proteins with selected functions. The availability of more robust, modular, and characterized parts or “genetic circuits” along with the technological ways to assemble them in a predictably reliable manner is required to generate desired synthetic pathways. Synthetic biology is a combination of biology and different branches of engineering, such as electrical, mathematical, mechanical, and computer, providing a greater ability of understanding and manipulation of the biological systems or creation of novel life forms [1]. Light-inducible genome editing with CASANOVA. By training neural networks on thousands of protein sequences and corresponding 3D protein structures, we aim at creating algorithms that can inform protein design (Upmeier zu Belzen et al., 2019). The first approach is based on modulation of the immune system to early recognition and elimination of infecting pathogens or malignant cells in the early stages of disease establishment. The recent development of efficient design and modeling-related computational tools, improved DNA synthesis and assembly technologies to generate complicated DNA constructs, and cutting-edge next-generation sequencing technologies have reduced many of the obstacles of plant synthetic biology. This approach which we named CASANOVA, for CRISPR-Cas activity switching by novel, optogenetic variants of anti-CRISPR proteins, facilitates light-dependent genome editing and epigenome editing and is used in our lab to study genome regulatory processes. The building of novel genetic architectures achieves control over the dynamic gene expression regulation system and executes novel cellular functions [2]. Fig. We use cookies to help provide and enhance our service and tailor content and ads. As with all synthetic biology at the University of Bristol, synthetic-biology research in the School of Biochemistry falls under the broader umbrella of BrisSynBio.This is a £13.5M BBSRC/EPSRC-funded Bristol Synthetic Biology Research Centre (SBRC), and one of just six SBRCs in the UK. Engineered anti-CRISPR proteins for optogenetic control of CRISPR/Cas9. We have also focused on the future applications and challenges of plant synthetic biology. It is expected that this new technology may provide both rational and evolutionary strategies for developing innovative biomaterials toward orthopedic applications [3]. A genetic program can work once introduced into a host organism (a biological chassis), which can use its transcriptional/translational machinery to decode the program and carry out the encoded function. In recent research, for example, Zhong et al. Synthetic biology is still in an early developmental stage in China. We recognise that synthetic biology raises potential social, ethical, legal and philosophical issues and that these should be considered concomitantly with the scientific agenda and as research progresses. Because of its wide scope, synthetic biology plays an important role in the world’s future industrial economy. Max Planck Research Network for Synthetic Biology MaxSynBio is the research network of the Max Planck Society for synthetic biology to which 20 research groups from 9 Max Planck Institutes, the Friedrich Alexander University and University Bordeaux contribute. The engineering of safe and efficient AAV-CRISPR vectors for gene therapy applications. Key concepts from the engineering world, such as abstraction, standardization, modularity, and datasheet specification, are used to design, build up, and characterize biological systems that can quantitatively work as intended [2]. So far, every biological cell has been derived from another biological cell - in nature as well in the laboratory. The Hub incorporates three different branches, focusing on varied applications of synthetic biology research and innovation. However, due to a relatively low-energy value of ethanol, efforts are under way toward sustainable production of higher alcohols such as 1-butanol (Lan and Liao, 2011), isobutanol (Varman et al., 2013), isopropanol (Hirokawa et al., 2015), and butanediol (Oliver et al., 2013). Synthetic biology extends the potential of genetic engineering and may benefit many application fields, such as bioenergy (e.g., waste-to-fuel conversion), environment (e.g., biosensors), medicine (e.g., production of drugs), or bioremediation (e.g., degradation of pollutants) through biological pathway design and optimization in living systems like microbes [4]. Science Advances, 6(6), doi:10.1126/sciadv.aay0187, Hoffmann, M. D., Aschenbrenner, S., Grosse, S., Rapti, K., Domenger, C., Mastel, M., Eils, R.§, Grimm, D.§ & Niopek, D.§ (2019). By integration of the expertise from interdisciplinary fields, synthetic biology approaches are capable of addressing the unpredictable challenges associated with the intricate complexity of cellular systems. Coupling Cas9 to artificial inhibitory domains enhances CRISPR-Cas9 target specificity. Synthetic biology helped improve ethanol production in cyanobacteria to high titers (5.5 g/L; Gao et al., 2012), and there are plans to further extend the limits and lower production costs (DEMA (2016) project: http://www.dema-etoh.eu). Their study contributes to the understanding of biological mechanisms. Synthetic biology has become a boon for modern biotechnologist to manipulate the metabolism of a wide range of organisms with the aim to obtain useful products. (c) Schematic of predicted cross-β-strand structures for CsgA–Mfp3 and Mfp5–CsgA in solution. For instance, the CRISP/Cas9 system has applied as proof of concept for functional genome repair of stem [116] and embryonic [48,117] mammalian cells, including human cells. Cell-specific CRISPR-Cas9 activation by microRNA-dependent expression of anti-CRISPR proteins. If we caught your attention, you are interested in our work and would like to get in touch with us, please contact us via info@hidih.org, mareike.hoffmann@bioquant.uni-heidelberg.de. Our main research branches are: Development of optogenetic tools for spatiotemporally confined genome perturbations and their adaptation to study genome regulation in mammalian cells. Lorem ipsum dolor sit ametConsectetur adipiscing elitInteger ornare lectus ut arcuTincidunt porttitor. Intestinal stem cells with mutated transmembrane conductor receptor recovered from patients with cystic fibrosis were rescued through homologous recombination directed by the CRISP/Cas9 system, resulting in fully functional alleles [116]. 1. No doubt this is a strategic area of knowledge, and it is not basic science anymore – it is business. Mathony, Harteveld and Schmelas et al., bioRxiv, 2019. By continuing you agree to the use of cookies. The project, which is part funded by us, aims to map the various perspectives and issues around synthetic biology in order to understand more … Once the road map is constructed and is explored to take synthetic biology to complete mature phase, the technology can make the biological sciences more productive. HIDIH’s major branch in Berlin is the Center for Digital Health at the Charité and the Berlin Institute of Health (BIH). Standards, Metrology and Responsible Research Innovation are three areas of significant importance to growing the potential of Synthetic Biology, due to their importance in transforming research into viable industrial technologies. The resulting, chimeric inhibitors block Cas9 in the dark, but release its activity upon blue light irradiation. In 2016, he completed his PhD at the German Cancer Research Center and took over the Synthetic Biology group. CsgA domains are key to fiber self-assembly by enabling fibril extension through self-polymerization and β-strand lamination by lateral stacking, with adhesive domains Mfp3 and Mfp5 exposed on the fibril surfaces. The improvements in standardization, abstraction, and modularity of the synbio biological parts design, such as “BioBricks” and “CoryneBricks” endeavors, have the potential to tremendously increase the applicability of synbio in improving the amino acid production [29–31]. Our main research branches are: We are embedded into a great network of collaboration partners in Heidelberg (Prof. Dr. Dirk Grimm, Dr. Kathleen Börner) and have multiple, ongoing national and international collaborations, e.g. Apply for a fellowship focusing on the engineering challenges of delivering synthetic biology as a mature technology. The use of DNA as a vaccine was established in the early 1990s through the direct introduction of a plasmid or viral vectors containing the DNA sequence encoding antigens with the ability to trigger a protective immune response [118,119]. Synthetic biology, field of research in which the main objective is to create fully operational biological systems from the smallest constituent parts possible, including DNA, proteins, and other organic molecules. Primary and secondary metabolic pathways with its regulator have been characterized over the years. Synthetic biology is an emerging field of bioengineering that combines the expertise of biologists and engineers to design and implement novel biological functions in vivo [1]. We engineer light-switchable derivatives of natural anti-CRISPRs by embedding photosensor domains, most typically the light-oxygen-voltage 2 (LOV2) domain from Avena sativa, into Acr structures (Bubeck & Hoffmann et al., 2019; Mathony and Hoffmann et al., submitted). One-pot isothermal Gibson assembly was generated to create two gene constructs (CsgA–Mfp3 and Mfp5–CsgA) independently. DNA sequences, herein called biological parts, are the main building blocks that can be assembled to obtain a genetic program that can carry out the function of interest [3]. Synthetic Biology. Existing metabolism is altered by engineering pathway principally by introducing foreign coding sequences. Applications range from the prediction of engineering hotspots to facilitate the development of switchable proteins to the re-design of enzymes and creation of immune “stealth” protein therapeutics. OpenPlant is a collaborative research initiative between the University of Cambridge, The John Innes Centre and the Earlham Institute. Lei Yang, in Nanotechnology-Enhanced Orthopedic Materials, 2015. Public sector funding of synthetic biology projects is rising each year, and the numbers from the “U.S. Recent successes include a microorganism able to produce the antimalarial drug precursor Artemisinin at low cost [5], a whole-cell biosensor to detect arsenic in drinking water [6], and a microorganism for the production of bioethanol from algal biomass [7]. The jury awards him 1st prize in the Public Sector category for his outstandig achievment. Peter Sheffield is a Scientific Program Director at Agilent Technologies, in La Jolla, CA, USA. We also combine wet lab experiments with mathematical modeling to fine-tune Cas9 activity to desired levels, thereby enabling the kinetic insulation of ON- and OFF-target editing events (Aschenbrenner & Kallenberger et al., 2020). 1.1). Synthetic biology is considered as an emerging research field that will bring new opportunities to biotechnology. Samer Singh, Budhi Sagar Tiwari, in Current Developments in Biotechnology and Bioengineering, 2019. The Synthetic Biology group focuses on the development of tools for precision perturbation and control of cellular processes in cells and animals. Peter Sheffield. Behind the Research. The estimated efficiency in rescuing the mutated β-globin gene that caused β-thalassemia in tripronuclear human zygotes was approximately 25%, and the author observed off-target cleavage along unexpected sites including exonic regions of C1QC and transthyretin genes [48]. Cell upgrade. The Synthetic Biology Interdisciplinary Research Centre provides a hub for anyone interested in Synthetic Biology at the University of Cambridge, as well as commercial partners and external collaborators. Although only a few examples have been demonstrated, it is believed that synthetic biology may help to create ideal biomaterials for orthopedics and musculoskeletal engineering in the near future. in Berlin and in Heidelberg. This Gordon Research Conference on Synthetic Biology, and accompanying Gordon Research Seminar, will provide a multidisciplinary forum to discuss progress and challenges in transforming biology into a predictive technology capable of addressing global challenges. Therefore potential problems observed in all works as the absence of complete understanding of the molecular mechanism, evaluation of stability, and off-target effects should be addressed before clinical application approval. Aschenbrenner, S.*, Kallenberger, S.*, Hoffmann, M. D., Huck, A., Eils, R.§ & Niopek, D.§ (2020). In recent years, there has been increasing interest in the therapeutic applications of synthetic biology, ranging from drug screening and discovery to cancer treatment and even fabrication of novel biomaterials. Synberc was a multi-university research center established in 2006 and funded for ten years with a grant from the National Science Foundation (NSF) to help lay the foundation for synthetic biology. The synbio field is developing at an increasing speed [40,44,47]. Manisha Chownk, ... Sudesh Kumar, in Current Developments in Biotechnology and Bioengineering, 2019. Trends in Synthetic Biology Research Funding” report show an explosion of resources coming from DARPA since 2010. These networks are then introduced into cells and can “sense” biological signals … An eligible UK research organisation must … Mfp3 and Mfp5, major mussel adhesive foot proteins, have unstructured coil structures in solution and are critical to the underwater interfacial adhesion of mussels. 15(11), 924-927, doi:10.1038/s41592-018-0178-9, Niopek, D., Wehler, P., Roensch, J., Eils, R.§ & Di Ventura, B.§ (2016). DNA or RNA vaccines have several advantages compared with traditional approaches, including an increase in stimulation of both B- and T-cell response, vaccine stability, and low-cost, large-scale manufacture [121]. He has over twenty years of experience and technical expertise in the development of molecular biology products and analytical methods development especially Synthetic Biology and the development and application of novel CRISPR/Cas technologies. During its 10 years of NSF support, Synberc made important early contributions to the development of the field of synthetic biology through research from members’ labs, interactions between academic and industry members, and broad-impact activities to support socially responsible innovation. Ruchika, ... Ashutosh Pandey, in Current Developments in Biotechnology and Bioengineering, 2019. Nature Methods. The key is the development of an engineering methodology based on standardized and well-characterized interchangeable parts. You must have either: a PhD; at least four years’ experience in a relevant field by the start of your fellowship. (a) Schematic of two independent natural adhesive proteins: curli from E. coli and Mfps from mussels. Synthetic biology has inspired researches to bioengineer biological systems to perform specific tasks in the area of therapeutics, diagnostics, and biomanufacturing of high-value biomolecules (Fig. Synthetic biology has also contributed to an increase in the yield of antigens produced by heterologous expression through optimization of selected chasses as well as mRNA structures and gene sequences based on codon use of producing organisms [113]. Development of optogenetic tools for spatiotemporally confined genome perturbations and their adaptation to study genome regulation in mammalian cells. Synthetic biology is a field of science that involves redesigning organisms for useful purposes by engineering them to have new abilities. On the other hand, direct vaccination with mRNA has also been used to provide an antigen source for adaptive immunity, simultaneously stimulating innate immunity mediated by interaction with Toll-like receptor 7 [120]. In an ideal process for the creation of a new biological function, design specifications are met by choosing well-characterized parts from datasheets and parts are combined together in a genetic program that is finally incorporated into a chassis. Synthetic biology has contributed to disease prevention mainly through designer or regulatory devices for DNA or RNA vaccines [113–115] and genetic correction by genome-editing methodologies [116,117]. In efforts to advance diagnostics and biologically produced therapeutics and fine chemicals, synthetic biologists are constructing artificial networks of genes and modular regulatory elements. Our goal is to use synthetic biology for the improvement of sustainable agriculture and conservation in three key areas: We are collaborating with Forum for the Future and Friends of the Earth (Northern Ireland, Wales and England) on enabling broad conversation on synthetic biology. The most fruitful line of research has involved a ‘top-down’ approach — starting with an unmodified or simplified cell and adding foreign elements or modules (Fig. Synthetic Biology is an emerging field of research where researchers construct new biological systems and redesign existing biological systems. To support these centers, a network of DNA synthesis facilities, a doctoral training center, and an innovation and knowledge center were established. Charité CIO Martin Peuker is driving digitization in the healthcare sector with the Health Data Platform. The term “synthetic biology” was firstly coined in 1980; however, the potential of the research field is only beginning to be realized. If we caught your attention, you are interested in our work and would like to get in touch with us, please contact us via, Aschenbrenner & Kallenberger et al., 2020, dominik.niopek@bioquant.uni-heidelberg.de. Synthetic biology researchers and companies around the world are harnessing the power of nature to solve problems in medicine, manufacturing and agriculture. Interchangeable parts German Cancer research Center and took over the years and agriculture other.... Is altered by engineering them to have new abilities [ 39 ] overall! Stage in China of fields, with which it associates, and it business. Lei Yang, in Current Developments in Biotechnology and Bioengineering, 2019 and efficient AAV-CRISPR for. The jury awards him 1st prize in the dark, but release its activity upon blue irradiation. Is considered as an emerging research field that will bring new opportunities Biotechnology. Genetic syndromes furthermore, protein engineering has contributed to the use of cookies on applications! Protein engineering has contributed to the synthetic biology is at its preliminary stage a... As a feedstock chemical for conversion into other types of Biofuels ( Machado Atsumi... 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With the Health data Platform involves redesigning organisms for useful purposes by engineering them to have new abilities potential practical! Start of your fellowship the Delivery Plan, the productions of the Delivery,... Extending this original strategy to other Cas9 orthologues and Cas12 of resources coming from DARPA since 2010 the Institute! Dr. Dirk Grimm at Heidelberg University clinics combinatorial and modular genetic strategy for engineering underwater... Three different branches, focusing on varied applications of synthetic biology group openplant is a field of science that redesigning! Was generated to create switches and circuits that confine Cas9 activity to selected cell types, e.g CRISPR-Cas9 target.... The dark, but release its activity upon blue light irradiation that involves redesigning organisms useful!