@article{KruegerFriedrichFoersteretal.2012,
  author    = {Krueger, Beate and Friedrich, Torben and F{\"o}rster, Frank and Bernhardt, J{\"o}rg and Gross, Roy and Dandekar, Thomas},
  title     = {Different evolutionary modifications as a guide to rewire two-component systems},
  series = {Bioinformatics and Biology Insights},
  volume    = {6},
  journal   = {Bioinformatics and Biology Insights},
  doi       = {10.4137/BBI.S9356},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-123647},
  pages     = {97-128},
  year      = {2012},
  abstract  = {Two-component systems (TCS) are short signalling pathways generally occurring in prokaryotes. They frequently regulate prokaryotic stimulus responses and thus are also of interest for engineering in biotechnology and synthetic biology. The aim of this study is to better understand and describe rewiring of TCS while investigating different evolutionary scenarios. Based on large-scale screens of TCS in different organisms, this study gives detailed data, concrete alignments, and structure analysis on three general modification scenarios, where TCS were rewired for new responses and functions: (i) exchanges in the sequence within single TCS domains, (ii) exchange of whole TCS domains; (iii) addition of new components modulating TCS function. As a result, the replacement of stimulus and promotor cassettes to rewire TCS is well defined exploiting the alignments given here. The diverged TCS examples are non-trivial and the design is challenging. Designed connector proteins may also be useful to modify TCS in selected cases.},
  language  = {en}
}
@phdthesis{Hell2019,
  author    = {Hell, Dennis},
  title     = {Development of self-adjusting cytokine neutralizer cells as a closed-loop delivery system of anti-inflammatory biologicals},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-175381},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2019},
  abstract  = {The current treatment strategies for diseases are assessed on the basis of diagnosed phenotypic changes due to an accumulation of asymptomatic events in physiological processes. Since a diagnosis can only be established at advanced stages of the disease, mainly due to insufficient early detection possibilities of physiological disorders, doctors are forced to treat diseases rather than prevent them. Therefore, it is desirable to link future therapeutic interventions to the early detection of physiological changes. So-called sensor-effector systems are designed to recognise disease-specific biomarkers and coordinate the production and delivery of therapeutic factors in an autonomous and automated manner. Such approaches and their development are being researched and promoted by the discipline of synthetic biology, among others. Against this background, this paper focuses on the in vitro design of cytokine-neutralizing sensor-effector cells designed for the potential treatment of recurrent autoimmune diseases, especially rheumatoid arthritis. The precise control of inducible gene expression was successfully generated in human cells. At first, a NF-κB-dependent promoter was developed, based on HIV-1 derived DNA-binding motives. The activation of this triggerable promoter was investigated using several inducers including the physiologically important NF-κB inducers tumor necrosis factor alpha (TNFα) and interleukin 1 beta (IL-1β). The activation strength of the NF-κB-triggered promoter was doubled by integrating a non-coding RNA. The latter combined expressed RNA structures, which mimic DNA by double stranded RNAs and have been demonstrated to bind to p50 or p65 by previous publications. The sensitivity was investigated for TNFα and IL-1β. The detection limit and the EC50 values were in in the lower picomolar range. Besides the sensitivity, the reversibility and dynamic of the inducible system were characterized. Hereby a close correlation between pulse times and expression profile was shown. The optimized NF-κB-dependent promoter was then coupled to established TNFα- and IL-1-blocking biologicals to develop sensor-effector systems with anti-inflammatory activity, and thus potential use against autoimmune diseases such as rheumatoid arthritis. The biologicals were differentiated between ligand-blocking and receptor-blocking biologicals and different variants were selected: Adalimumab, etanercept and anakinra. The non-coding RNA improved again the activation strength of NF-κB-dependent expressed biologicals, indicating its universal benefit. Furthermore, it was shown that the TNFα-induced expression of NF-κB-regulated TNFα-blocking biologics led to an extracellular negative feedback loop. Interestingly, the integration of the non-coding RNA and this negative feedback loop has increased the dynamics and reversibility of the NF-κB-regulated gene expression. The controllability of drug release can also be extended by the use of inhibitors of classical NF-κB signalling such as TPCA-1. The efficacy of the expressed biologicals was detected through neutralization of the cytokines using different experiments. For future in vivo trials, first alginate encapsulations of the cells were performed. Furthermore, the activation of NF-κB-dependent promoter was demonstrated using co-cultures with human plasma samples or using synovial liquids. With this generated sensor-effector system we have developed self-adjusting cytokine neutralizer cells as a closed-loop delivery system for anit-inflammatory biologics.},
  subject      = {Biologika},
  language  = {en}
}
@article{BencurovaAkashDobsonetal.2023,
  author    = {Bencurova, Elena and Akash, Aman and Dobson, Renwick C.J. and Dandekar, Thomas},
  title     = {DNA storage-from natural biology to synthetic biology},
  series = {Computational and Structural Biotechnology Journal},
  volume    = {21},
  journal   = {Computational and Structural Biotechnology Journal},
  issn      = {2001-0370},
  doi       = {10.1016/j.csbj.2023.01.045},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-349971},
  pages     = {1227-1235},
  year      = {2023},
  abstract  = {Natural DNA storage allows cellular differentiation, evolution, the growth of our children and controls all our ecosystems. Here, we discuss the fundamental aspects of DNA storage and recent advances in this field, with special emphasis on natural processes and solutions that can be exploited. We point out new ways of efficient DNA and nucleotide storage that are inspired by nature. Within a few years DNA-based information storage may become an attractive and natural complementation to current electronic data storage systems. We discuss rapid and directed access (e.g. DNA elements such as promotors, enhancers), regulatory signals and modulation (e.g. lncRNA) as well as integrated high-density storage and processing modules (e.g. chromosomal territories). There is pragmatic DNA storage for use in biotechnology and human genetics. We examine DNA storage as an approach for synthetic biology (e.g. light-controlled nucleotide processing enzymes). The natural polymers of DNA and RNA offer much for direct storage operations (read-in, read-out, access control). The inbuilt parallelism (many molecules at many places working at the same time) is important for fast processing of information. Using biology concepts from chromosomal storage, nucleic acid processing as well as polymer material sciences such as electronical effects in enzymes, graphene, nanocellulose up to DNA macram{\´e} , DNA wires and DNA-based aptamer field effect transistors will open up new applications gradually replacing classical information storage methods in ever more areas over time (decades).},
  language  = {en}
}