RNA is common to all organisms. Despite its major function as the coding agent for protein synthesis, an increasing number of regulatory roles have been assigned to RNA. In bacteria, small RNAs (sRNAs) constitute the best-studied class of non-coding regulators estimated to control ~20% of all genes in a given organism. Most sRNAs affect gene expression by base-pairing with multiple target mRNAs resulting in either gene repression or activation. sRNA regulators are modular, versatile, and highly programmable, and thus have gathered momentum as control devices in synthetic biology and biotechnology. My group has recently established artificial sRNAs as a potent genetic tool to screen, detect, and characterize microbial phenotypes. We have now extended this method by a novel sequencing approach, called LIGseq, allowing us to map sRNA-target interactions at the population level and in a high throughput manner. We have further shown that sRNAs expressed from the 3’ untranslated regions (UTRs) of mRNAs can serve as tuneable autoregulatory elements and thus bear ample possibilities for the design of artificial gene networks. I therefore posit that artificial sRNAs are powerful, yet understudied control elements of the synthetic biology toolbox with largely untapped regulatory potentials. I thus propose to: 1) exploit artificial sRNAs to investigate the molecular principles underlying target selection and RNA duplex formation by bacterial non-coding RNAs, 2) harness the power of artificial sRNAs to study essential gene functions and the mechanisms underlying antibiotic resistance in bacteria, 3) employ 3’UTR-derived sRNAs as programmable feedback devices in synthetic gene regulatory circuits. This combined work will generate the molecular framework to employ artificial sRNAs for synthetic biology applications and shed new light on medically relevant processes, such as antibiotic resistance of microbial pathogens.

This research project, CARMESilk, aims to develop an innovative solution for preventing chemotherapy-induced alopecia (CIA) to improve cancer patients' quality of life. CIA is one of the most distressing side effects of cancer, affecting up to 65% of cancer patients undergoing treatment, causing social withdrawal, decreased self-esteem, and depression. Doxorubicin, a chemotherapeutic agent from the group of anthracyclines, is used as cancer drug in breast, ovary, bladder, and thyroid cancers, among others, and it has an incidence of CIA of 60-100%. Current therapies focus mainly on scalp cooling technology with limited availability, high cost, long-time treatment, and not recommended for children. For this reason, the development of effective CIA prevention technologies has the potential to be truly life-changing for cancer patients by alleviating the psychological distress associated with treatment and by empowering patients to maintain a sense of normalcy and control during a challenging period. CARMESilk, aims to create a novel, patient-friendly technology, silk fibroin-based, that selectively captures doxorubicin within the hair matrix, via minimally invasive routes, thereby preventing hair loss while still maintaining chemotherapy efficacy. The fabrication of a 3D bioprinted scalp model using human hair follicles will establish the way for personalized CIA prevention strategies. CARMESilk is an interdisciplinary project combining nanotechnology, materials science, and bioengineering with a patient-centric approach. The project, as a Global fellowship, will be performed over three years, in US (2 years) and in Germany (1 year), with experts in the tissue engineering field. The achievement of CARMESilk goals will represent an improvement in patients' quality of life, a proof of concept of the technology that can be applied to other chemotherapy agents, highly impacting CIA prevention during an already challenging period.

Glasses have traditionally been enabling materials to major societal challenges. Significant breakthroughs on many areas of technological progress have been very closely linked to the exploitation of glassy materials. It is strong consensus that this key role will persist in the emerging solutions to major global challenges in living, energy, health, transport and information processing, provided that the fundamental limitations of the presently available empirical or semi-empirical approaches to glass processing can be overcome. In the coming decade, it is therefore a major task to take the step towards ab initio exploitation of disordered materials through highly-adapted processing strategies. This requires pioneering work and in-depth conceptual developments which combine compositional design, structural evolution and the thermo-kinetics of material deposition into holistic tools. Only those would significantly contribute to solving some of the most urgent materials needs for glass applications in functional devices, be it in the form of thin films, particles or bulk materials. The present project challenges today’s engineering concepts towards the conception of such tools. For that, melt deposition, isothermal deposition from liquid phases, and gas-phase deposition of non-crystalline materials will be treated - within the class of inorganic glasses - in a generalist approach, unified by the understanding that glass formation represents the only strict deviation from self-organization, and that, hence, the evolution of structural complexity in glassy materials can be tailored on any length-scale through adequate processing. Providing a topological scheme for the quantification and chemical tailoring of structural complexity, UTOPES will answer to the challenge of finding order in disorder, and will thus break the grounds for the third generation of glasses with properties beyond what is presently thought as the limits of physical engineering.