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.

Ultrafast lasers, which allow the concentration of light in space and time, have been instrumental in revolutionizing industrial production technologies, medical applications and cutting-edge fundamental research. A common demand for many applications is the combination of maximum pulse peak powers with maximum average powers, in extreme cases involving petawatt (PW) peak powers and megawatt (MW) average powers. Additionally, these parameters must be achieved together with an optimum beam quality and high efficiency. The MIMAS project aims to address these demands and enable new realms of performance for ultrafast lasers. The basic idea is spatially and temporally separated amplification of ultrashort laser pulses followed by coherent combination. This overcomes all the scaling limitations known in single-emitter systems. Moreover, the spatially separated amplification will be developed to an integrated and highly compact configuration: an ytterbium-doped multicore fiber. In addition, it is proposed that a sequence of pulses be amplified with an encoded phase pattern, causing a coherent pulse stacking at the system output. The targeted laser pulse parameters are completely beyond the scope of current laser technology and therefore able to revolutionize many applications. The target is to generate a pulse energy of >1J at 10kHz repetition rate, i.e. an average power of >10 kW, with a wall-plug efficiency of >10%. Together with a pulse duration of 5 TW in a scalable architecture. This outstanding performance, which is three orders of magnitude above the capabilities of today’s laser systems, is emitted from only two fibers and features excellent beam quality. I am deeply convinced that such an ultrafast laser source will be the key element in a number of experiments in modern sciences; not only in fundamental physics but also in biology and medicine, it will stimulate seminal discoveries and breakthroughs.