12 PhD positions within the MSCA Doctoral Network “SYNSENSO”: Cell-free synthetic biology for combinatorial biosensor design:

The Doctoral Network SYNSENSO “Cell-free synthetic biology for combinatorial biosensor design”, funded within the framework of the Marie Skłodowska-Curie Actions (MSCA), follows an interdisciplinary and cross-sectoral approach by bringing together academic and industrial experts from the fields of cell-free synthetic biology and molecular sensor design to develop novel combinatorial biosensors. 

Five academic research groups and two industrial partners, coordinated by Technische Universität Darmstadt in Germany, join forces in SYNSENSO to create a mobility and training platform for young scientists by means of cross-site, interdisciplinary research projects. The PhD students will work on individual research projects in order to devise new logic circuits in cell-free systems,  build novel responsive elements for analyte detection and integrate logic circuits with response elements to build and test next-generation, combinatorial biosensors.

The specific research projects at the different groups are listed below. In addition to the host institutes (see below), the consortium also includes associated academic and industrial partners (Imperial College London (UK), Nuclera Nucleics Ltd. (UK), BioMerieux SA (France), LenioBio GmbH (Germany), BRAIN Biotech AG (Germany), Advance Biotech (Spain)), which are available for secondments and collaborations.

Candidate profile:

  • MSc, MRes, MEng, or equivalent in Life Science (Biology, Biochemistry, Biophysics, etc), Bioengineering, Physics or a related discipline
  • Wet-lab experience, in particular with genetic engineering or molecular biology
  • Interested to work in the field of synthetic biology
  • Appreciation for interdisciplinary work and proactive drive to collaborate across disciplines
  • proficient in English language

Enrolment, eligibility, salary:

  • Applicants must have obtained their masters degree and must not have a doctoral degree at the date of their recruitment
  • Applicants should not have been living in the country of the host institution for which they are applying for more than 12 months in the last 3 years (exception: refugee status). Applicants can be of any nationality.
  • Subject to the successful signing of the EU Grant Agreement, SYNSENSO is planned to start with 01.09.2022 and the start of the individual doctoral project should be between 01.09.2022 and 31.03.2023.
  • The successful candidate will receive a financial package including mobility and family allowance (if applicable), and will be employed according to the rules for Early Stage Researchers in an Marie Skłodowska-Curie Actions Doctoral Network (DN) and the general regulations of each host institution.
  • The MSCA-DN will cover 3 years of full-time research. Final contract length and extension options depend on the host institution.

Application:

  • Applications should include a motivation letter, CV, copy of transcripts and of obtained degree and contact details of 2 references.
  • Applicants should provide a ranked list of projects they are most interested to work on.
  • Please send your application via email: synsenso@bcs.tu-darmstadt.de
  • Application deadline: 15.08.2022.

Doctoral Projects:

DC1 – Cell-free RNA-based logic circuits, Host: Prof. Heinz Koeppl, Technische Universität Darmstadt, Germany

Within this project energy-efficient RNA-based gates that can be cascaded will be designed and used as combinatorial sensors for long-noncoding RNAs.

DC2 – Machine-learning based design and optimization of analyte-responsive ribozymes,

Host: Prof. Beatrix Suess, Technische Universität Darmstadt, Germany

The goal of this project is to increase the sensitivity and specificity in the detection of analyte molecules through optimized ribozymes. Thereby neuronal networks will be used to enable faster and more cost-effective identification of suitable linker sequences for interesting analysis by reducing the need for time-consuming laboratory tests.

DC3 – CRISPR-based RNA editing tools for cell-free biosensors, Host: Prof. Tom de Greef, Eindhoven University of Technology, Netherlands

Within this project a cell-free platform based on integration of the newest generation of computationally designed CRISPR effectors will be developed, that allow programmable RNA-guided RNA cleavage. This will be used for combinatorial sensor system for the detection of disease-associated micro-RNAs.

DC4 -Modeling and simulation of cell-free synthetic circuits, Host: Prof. Tom de Greef, Eindhoven University of Technology, Netherlands

The doctoral candidate will explore design principles for logic gates utilizing co-localization of regulatory RNA elements at the nanoscale. Within this project a cell-free platform based on integration of DNA origami nanostructures with E. coli will be developed.

DC5 – Enhanced cell-free lysates with pre-expressed regulators, Host: Prof. Heinz Koeppl, Technische Universität Darmstadt, Germany

This project is dedicated to taking cell-free lysates to the next level: overcoming the energy-limitation of cell-free lysates enabling more complex biosensors; understanding resource competition in bacterial production strains through expression of a regulator palette; minimize batch variability and maximum efficacy of regulators within the cell-lysate.

DC6 – Cell-free responsive elements and biosensors for DNA repair enzymes, Host: Prof. Francesco Ricci, Tor Vergata Universita degli Studi di Roma, Italy

Within this project a cell-free biosensors for DNA repair enzymes will be developed Thereby the candidate will work on novel programmable DNA/RNA elements responsive to different DNA repair enzymes; cell-free transcription of different RNA sequences achieved with different DNA repair enzymes, orthogonal cell-free circuits responsive to DNA repair enzymes.

DC7 – RNA-binding proteins for circuit design and detection of viral infection, Host: Dr. Velia Siciliano, Istituto Italiano di Technologia, Naples, Italy

The doctoral candidate will evaluate new RNA-binding tools for translational control and for Boolean logic gates in cell-free systems. The goal is to apply the research results to a general-purpose platform for protease-based detection viral infection and to develop a low-cost paper-based biosensor for rapid infection detection.

DC8 –  DNA/RNA responsive elements for cell-free biosensors, Host: Prof. Francesco Ricci, Tor Vergata Universita degli Studi di Roma, Italy

This research project will explore novel DNA/RNA responsive elements with programmable and controllable input/output behaviour to reach a tuneable dynamic range by using different intrinsically disordered regions and eventually achieve digital-like response of DNA/RNA circuits with transient and reversible activation of responsive DNA/RNA elements.

DC9 – Cell-free synthesis of RNA aptamers on a biochip, Host: Dr. Ralf Strasser, Dynamic Biosensors GmbH, Munich, Germany (PhD awarded from TU Darmstadt)

Within this application-oriented project the doctoral candidate will evaluate cell-free expression systems for their use on biochips. The focus here is on improving assays for detection of conformational changes of RNA aptamers and the development of general method for attaching a recognition element to DNA using cell-free systems.

DC10 – Cell-free responsive elements for antibodies and proteins detection, Host: Dr. Bruna Marini, Ulisse Biomed GmbH, Udine, Italy (PhD awarded from Tor Vergata Universita degli Studi di Roma)

Within this project a DNA/RNA responsive element with fluorescent detection for trastuzumab (mono-specific antibody), blinatumomab (bi-specific antibody) and EGFR will be developed. Thereby an orthogonal optical detection of all three targets in the same solution should be achieved.

DC11 – Intein-based logic gates for multiplexed designs, Host: Prof. Karen Polizzi, Imperial College London, UK (will be funded through the UKRI Horizon Europe Guarantee Funding Scheme)

The work on this project includes the development of novel design principles for fast protein-based logic gates. Thereby an intein toolbox with well-characterized parts will be optimized for cell-free systems and the kinetics of intein splicing under different reaction conditions will be evaluated.

DC12 – Developing phosphorylation cascades in cell-free circuits, Host: Prof. Karen Polizzi, Imperial College London, UK (will be funded through the UKRI Horizon Europe Guarantee Funding Scheme)

The goal of the project is to establish new mechanism for harnessing the diversity of two-component signalling systems for biosensors in cell-free systems. A set of well-characterized parts for implementing phosphorylation cascades in cell-free systems should be developed and applied on a prototypical design of a fast biosensor for antimicrobial peptides.

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