This European Training Network (ETN) entitled “Chemical Reaction Networks: Signal amplification, spatiotemporal control, and materials” (CReaNet) will train 15 bright early-stage researchers (ESRs) on the emerging topic of chemical reaction networks (CRNs) that is currently lacking in the university curricula.
Early Stage Researcher (PhD) projects
WORKPACKAGE 1: CRNs for ultrasensitive amplification.
Sensitive detection of biotics (e.g., viruses, proteins, antibodies, DNA, and RNA) or controlled substances (i.e., drugs or explosives) is of key importance in research, industry, and public safety. Direct detection using chromatographic techniques (e.g. LC-MS or GC-MS, liquid/gas chromatography coupled to mass spectrometry) is increasingly possible at medium to low analyte concentrations, but this approach is not feasible for trace amounts. To this end, indirect detection is used, relying on amplification techniques, where a trace amount of analyte induces an increase in a second (easily detectable) molecule. The most prolific of the indirect biotic detection methods are immunoassays (e.g., ELISA, fluorescence, colorimetric, etc.). The ELISA assay leads to a linear increase in output signal (i.e., colour). However, boosting sensitivity requires finding pathways going from linear to non-linear processes. Other methods such as exponential rolling circle amplification (a special DNA-PCR polymerase chain reaction method) and other well-designed CRNs can lead to amplification processes beyond linearity. In this WP, we use different experimental and theory approaches to achieve non-linear amplification using CRNs. We make use of instabilities arising from non-linear kinetics, or by using cascades of chemical reactions.
The objective is to develop a CRN to achieve ultrasensitive analyte detection to be used on a subject under forensic investigation in real time and on-site or in vivo. An oxidase (enzyme) will be placed in the core of a microbead, which upon selective oxidation of the analyte generates a stoichiometric amount of hydrogen peroxide. In the second step, the peroxide will trigger a chemical amplification sequence of boronic phenol esters located in the shell of the bead, resulting in an exponential amplification of the peroxide. The peroxide will reach its target dye molecules at the outer surface of the gel beads to give the desired colour change. In other words, a reaction cascade from core to shell is responsible for the amplification. The main innovative features of this system are (i) the on-site sequestering of analytes by the microporous gel beads, (ii) the application of enzymes to achieve analyte selectivity, (iii) the immobilisation of the chemical amplification reaction in microbeads to ensure fast and spatially coordinated reactions and to facilitate colour detection by maintaining high local concentrations, and (iv) the spatial organisation of the chemical amplification system in compartmentalised beads to separate incompatible reactants. ESR1.1 will (i) fabricate the compartmentalised gel microbeads with the chemical amplification components, (ii) explore the relation between spatial organisation within the bead, amplification efficiency and sensitivity (secondment at TUD), (iii) develop numerical models for a quantitative description and analysis (secondment at USFD), and (iv) explore the boundary conditions for on-site trace detection in forensic (fingerprints, hazards) and biological samples. |
Supervisor | Name :Marcel de Puit Email :m.de.puit@nfi.nl Website :www.forensicinstitute.nl, marceldepuit.com |
Host Institution | Netherlands Forensic Institute Laan van Ypenburg 6 2497 GB The Hague The Netherlands |
Required profile | · You have at least a MSc in a relevant area of expertise, such as organic (synthetic) chemistry, ideally with experience in soft matter. · You have a strong interest in bio-organic chemistry and bio-engineering and molecular analysis. · Affinity with computer modelling or experience with computational and/or physical chemistry are a plus. · A secondment at the University of Sheffield is planned in the second year of the contract. |
Cell signalling is constantly occurring in natural biological systems in order to self-regulate responses and actions.[1] Ultrasensitivity plays an important role in signal transduction enhancing the output (response) when a minimal input (perturbation) is given. Phosphorylation/dephosphorylation cycles can exhibit ultrasensitivity due to different mechanisms such as: i) multisite phosphorylation, ii) positive or negative feedbacks loops, or iii) and 0th–order ultrasensitivity.[2] The latter mechanism occurs when the enzymes are working in a saturating environment with respect to the substrate resulting in a (ultrasensitive) sigmoidal response with respect to the substrate that is phosphorylated.[3] Our goal is to use phosphorylation/dephosphorylation of a short peptide (i.e., kemptide) to obtain ultrasensitivity in an artificial system. Specifically, we propose to prepare dissipative (non-equilibrium) steady states of kemptide (Leu-Arg-Arg-Ala-Ser-Leu-Gly, containing a serine residue) that can be phosphorylated upon the addition of adenosine-5’-triphosphate (ATP). Upon application of a stimulus (variation in ATP concentration), the system can react to give a transient alteration (returning to the previous level), partial adaption (change to another steady-state), or changes to the steady-state without adaptation period. Models of this CRN will be developed (during the first secondment), and together we will investigate to use this ultrasensitive CRN to detect (possibly forensically) relevant signals.
[1] Goldbeter, A. & Koshland, D. E., J. Biol. Chem. 1984, 259, 14441-14447.
[2] Martins, B. M. C. & Swain, P. S., PLOS Comput. Biol. 2013, 9, e1003175.
[3] Ferrell, J. E. & Ha, S. H., Trends Biochem. Sci. 2014, 39, 496–503.
Supervisor | Name : Thomas HERMANS Email : hermans@unistra.fr Website : www.hermanslab.com |
Host Institution | University of Strasbourg Institut de Science et d’Ingénierie Supramoléculaires 8 allée Gaspard Monge 67000 Strasbourg, France |
Required profile | The candidate should hold a MS degree in (Physical or Supramolecular) Chemistry, ideally with a strong interest in self-assembly, complex systems, reaction networks. Interest for interdisciplinary research is important. Research stays are planned at the Netherlands Forensic Institute (the Netherlands) and the University of Sheffield (UK). |
This project will examine signal detection and amplification of catalytic chemical reaction networks (CRNs) confined in micro- or nano- compartments. Simulations of chemical reaction networks involving feedback (ODEs) will be tuned to display “on-off” signal response curves and the results will be used to enhance robustness and sensitivity of enzyme-based sensors in experiments. The project will involve three month secondments at the Weizmann Institute of Science (Israel) to examine nano-particle confinement and three months at the Netherlands Forensic Institute (NFI) to investigate enzyme-gel beads.
Supervisor | Name : Annette Taylor Email : a.f.taylor@sheffield.ac.uk Website :www.sheffield.ac.uk/cbe |
Host Institution | Department of Chemical and Biological Engineering, The University of Sheffield, UK |
Required profile | The post holder should have a good undergraduate degree (Bachelors or Masters level) in Chemical Engineering, Computer Science, Applied Mathematics, Chemistry or related discipline (BEng, MEng, BSc, MSc or equivalent qualification at 2.1, or equivalent, classification). This should be obtained by 1 September 2019. At the time of recruitment, 1 September 2019, you should be in the first 4 years of your research career (full-time equivalent research experience) and have not been awarded a doctoral degree and you must not have resided or carried out your main activity (work, studies etc) in the UK for more than 12 months in the 3 years immediately prior. You should also have some experience of chemical kinetics and/or solving differential equations using numerical simulations; however, training will be given in both of these areas. . |
Temperature induced fluorescence intensity change (TRIC) devices use temperature sensitive fluorescent dyes as a nanoscope to probe molecular properties and biomolecular interactions. TRIC enables to measure all-optical with a low material consumption, a very high throughput and in real time, thus making this technology a promising candidate for ELISA-like applications. NANOT is currently aiming to enter this emerging market and launch TRIC biosensors to mainstream bioanalytics. TRIC detection responds sensitively to changes at the surface of molecules and fluorescence intensity can be manipulated (e.g. strongly enhanced) by nobel metals like gold and by the proximity of chemical moieties like DNA. We therefore aim to explore different methods to achieve non-linear signal amplification by coupling a CRN to ELISA assays by i) functionalizing gold nanoparticles (Au NPs) with specific anti-analyte antibodies, or ii) by using antibody-ss-DNA conjugates to facilitate rolling circle amplification (RCA). Due to the high local electric fields at the Au NPs (i) or the increase of local DNA-concentration and mass (ii), a massive (> linear) increase in TRIC detection could be achieved. Additionally AU NPs with immobilized DNA can be used as a scaffold to connect the Au NPs (i) approach with the RCA (ii) approach. The RCA will be carried out in collaboration and through a secondment with ALU-FR. Continuous and non-continuous flow microfluidic ELISAs will be developed in collaboration and through a secondment at UNISTRA.
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WORKPACKAGE 2: Spatiotemporal control over CRNs.
Nature manages to get exquisite control over the location where CRNs can operate. For example, during cell division the Min system localises the exact center of the cell, using a reaction–diffusion process.[1] More generally, the patterns seen in animal prints can be traced back to reaction–diffusion instabilities of promotors and inhibitors.[2] In addition to passive transport, active (cilia-driven) fluid flows coupled with signalling give rise to the left-right organisation of internal organs (i.e., the heart on the left side).[3] In this WP2 we explore a range of spatiotemporal implementations of CRNs using compartmentalisation, passive/active transport within those compartments, and localised surface chemistries. In this way, we can engineer instabilities that arise from reaction–diffusion/advection. The goal of WP2 is to achieve spatiotemporal control over CRNs to mimic signalling, and to turn CRNs on/off in well-defined locations and times.
[1] Loose, M.; Fischer-Friedrich, E.; Ries, J.; Kruse, K.; Schwille, P. Science 2008, 320 , 789.
[2] Turing, A. M. Philos. Trans. R. Soc. B Biol. Sci. 1952, 237, 37.
[3] Sampaio, P.; Ferreira, R. R.; Guerrero, A.; Pintado, P.; et al. Dev. Cell 2014, 29, 716.
The complex biochemical reactions which serve to convey a signal occur at very precise time and place. During this PhD, we will build a microfluidic platform allowing the precise spatiotemporal control of biochemical networks. To reproduce chemical oscillations, we will implement continuously stirred tank reactors (CSTR) on a microfluidic chip. First, a single µCSTR will be designed and its mixing efficacity will be characterized. Then, up to 6 µCSTRs will be coupled in the same device, and the stability of the whole system will be studied depending on the µCSTRs location and their interactions. The flow management, the concentration of reagents, and the spatial distribution of the µCSTRs will be optimized both theoretically and experimentally. In the second part of the work, in collaboration with Chalmers and the University of Sheffield, we will study the signal transduction along this microfluidic device. To that aim, we will focus first on the methylene glycol-sulfite reaction to induce pH oscillations inside the system. Once it will be validated, we will implement a biocompatible oscillator on chip and study the signal transmission from one µCSTR to another, using for example the thiol/thioester exchange. |
Two secondments in partner universities are planned (around 3 months each).
PhD student will be enrolled at the University of Strasbourg.
Supervisor | Name : Noémi Thomazo Email : noemi.thomazo@elvesys.com Website : www.elvesys.com |
Host Institution | Elvesys – Microfluidics Innovation Center |
Required profile | A PhD at Elvesys will have nothing to do with a typical PhD. You will be immersed in a start-up with a strong entrepreneurial and innovative spirit. You will start your PhD with three months of entrepreneurship. Your mission: bring to the market a new product. This experience will allow you to learn entrepreneurship basis. After these 3 months of training you will continue working on an entrepreneurial project in parallel to your scientific project. Your background: A master degree/level in “hard science” (whether it is chemistry, physics, biology, microfluidics…) Your personality: You like to think “outside the box”, to be put out of your comfort zone. You would like to take up the challenge of doing a lot with little. You are able to adapt yourself quickly in a changing environment. You have team spirit and like to share your scientific problematics with a multicultural and diverse environment. |
The project is aimed at the preparation and characterization of soft matter chemical reaction networks, using microfluidic and 2D nanofluidic technology. The project is focused on phospholipid structures, such as nanotubes, vesicles and supported membranes on engineering surfaces, and uses microfluidic devices for preparation, sensing and manipulation. Preparation of functionalized lipid structures, measurement of properties and characterization of the structures by means of optical techniques, and development and fabrication of microfluidic chip devices. The Phd candidate receives comprehensive training in interdisciplinary research, analytical chemistry, microengineering includig cleanroom technologies, and data analysis.
| Supervisor | Name : Aldo Jesorka Email : aldo@chalmers.se Website : https://www.chalmers.se/en/staff/Pages/aldo-jesorka.aspx |
| Host Institution | Biophysical Technology Laboratory Department of Chemistry and Chemical Engineering Chalmers University of Technology Kemivägen 10, SE-41296 Göteborg Sweden |
Required profile
| – Completed MSc or equivalent degree in physics, physical chemistry or materials science – Practical knowledge of, and interest in soft matter – Hands-on knowledge of optical microscopy and related techniques – Working programming knowledge for image analysis and device control (Matlab, Phython or similar) – Successfully completed programming education during undergraduate studies is meritorious – Experience with measurement and characteriation of soft matter interfaces is of advantage To be succesful you need to be independent, self-motivated, ambitious, and willing to travel within Europe. As Chalmers is a highly international workplace, an advanced level of English in reading, writing and speaking is required. The candidate is expected to develop original scientific concepts, based upon the project framework, and communicate the results of this research. The position generally also includes teaching on Chalmers undergraduate level, or performing other equivalent duties corresponding to maximum of 20 percent of working hours. The PhD work requires travel and extended research visits in several European academic and commercial laboratories. |
DNA offers unique opportunities in the design of precision molecular switches and in the design of reaction networks that run either on DNA alone or are assisted by enzymes. When interfacing these intelligent DNA modules with synthetic polymers and polymer-colloids, significant opportunities arise for the design of complex systems as well as materials. Many of the complex fundamental issues in DNA nanotechnology have been successfully tackled, and tailor-made sequences and enzymes are commercially available or can be synthesized easily. It is thus very efficient and timely to implement these motifs for programmable systems and materials design, and open new horizons for non-equilibrium and life-like matter. This project will engage in the design of DNA-functionalized and DNA-based hydrogel particles/microgels and coacervates, and develop routines using (i) molecular photoswitches, (ii) chemically fueled enzymatic reactions and (iii) simple DNA computational algorithms to drive the systems towards transient colloidal assemblies with fuel-dependent lifetimes and self-sorting multicomponent systems mimicking more closely compartmentalization in cells. Additionally, simplistic artificial cells shall be constructed that harbor catalytic reactions to generate metabolic activity. You, as ESR, will learn on a synthetic side to master advanced polymer colloid chemistry, convenient DNA click reactions and the handling of enzymatic reaction cocktails. On an analytical side, you will become an expert in advanced optical microscopy techniques, such as confocal fluorescence microscopy, electron microscopy, dynamic light scattering, and in in-situ operated spectroscopic techniques such as light-coupled UV-VIS/fluorescence/NMR spectroscopy. The project is strongly interdisciplinar and connects polymer and colloid science with systems chemistry, DNA nanoscience and non-equilibrium self-assembly/physical chemistry. Two international secondments are foreseen to the US and to a European SME. Selected recent references on the topic: 1. “Antagonistic Enzymes in a Biocatalytic pH Feedback System Program Autonomous DNA Hydrogel Life Cycles” Nano Lett. 17, 4989 (2017). 2. “Materials Learning from Life: Concepts for Active, Adaptive and Autonomous Molecular Systems” Chem. Soc. Rev. 46, 5588 (2017). 3. “Social Self-Sorting of Colloidal Families in Co-Assembling Microgel Systems” Angew. Chem. Int. Ed. 56, 1521 (2017) 4. “Biocatalytic Feedback-Driven Temporal Programming of Self-Regulating Non-Equilibrium Peptide Hydrogels” Angew. Chem. Int. Ed, 54, 13258 (2015). 5. “Pathway-Controlled Formation of Mesostructured all-DNA Microgels and their Superstructures” Nat. Nanotech., 13, 730 (2018). |
Supervisor | Name: Prof. Dr. Andreas Walther Email: andreas.walther@makro.uni-freiburg.de Website: www.walther-group.com |
Host Institution | Institute for Macromolecular Chemistry, University of Freiburg, Germany. |
Required profile | As an ideal candidate you are creative, highly self-motivated, ambitious and communicative, and have obtained a M.Sc. degree in chemistry or a closely related discipline. A previous knowledge and hands-on expertise polymer synthesis, polymer materials or molecular systems is highly desirable. We stand ready to teach you more! A keen interest in the combination of fundamental sciences with applications, advanced analytics (in particular microscopy) and the will to work in an interdisciplinary and multinational program is an important prerequisite. |
This project will involve the investigation of spatial arrays of chemical reaction networks (CRNs) in micro or nano-compartments that are diffusively coupled through channels and/or a surrounding solution. Computational (PDE) models will be developed to aid in the experimental design of active spatially-structured materials. This project will involve three month secondments in the implementation of coupled CRNs at ELVESYS microfluidics (France) exploiting μCSTR arrays and the spatial translation of chemical signals to materials at the Delft University of Technology (Netherlands).
The position will be with Dr Annette Taylor in the Department of Chemical and Biological Engineering.
The ESR must enroll onto a PhD programme at the University of Sheffield and will spend 6 months on secondment at partner institutes.
The post holder should have have, or expect to have by 1 September 2019, an Undergraduate degree in Chemical Engineering, Computer Science, Applied Mathematics, Chemistry or related discipline. You should have some experience of chemical kinetics and/or solving differential equations using numerical simulations; however, training will be given in both of these areas.
Supervisor | Name : Annette Taylor Email : a.f.taylor@sheffield.ac.uk Website :www.sheffield.ac.uk/cbe |
Host Institution | Department of Chemical and Biological Engineering, The University of Sheffield, UK |
Required profile | The post holder should have a good undergraduate degree (Bachelors or Masters level) in Chemical Engineering, Computer Science, Applied Mathematics, Chemistry or related discipline (BEng, MEng, BSc, MSc or equivalent qualification at 2.1, or equivalent, classification). This should be obtained by 1 September 2019. At the time of recruitment, 1 September 2019, you should be in the first 4 years of your research career (full-time equivalent research experience) and have not been awarded a doctoral degree and you must not have resided or carried out your main activity (work, studies etc) in the UK for more than 12 months in the 3 years immediately prior. You should also have some experience of chemical kinetics and/or solving differential equations using numerical simulations; however, training will be given in both of these areas. . |
This project will focus on developing a novel, general methodology allowing for the remote modulation of chemical reaction networks using light. Such external control of reaction networks will be possible by introducing light-switchable nanoparticles to the system. These light-switchable nanoparticles will be composed of nanocrystalline inorganic (gold, silver, palladium, etc.) cores functionalized with monolayers of azobenzene-based photochromes. Photoisomerization of azobenzenes will control the self-assembly of nanoparticles. Recently, our group has demonstrated that as photoresponsive nanoparticles assemble in response to light, they can efficiently trap selected molecules. The light-induced disassembly of nanoparticle aggregates re-introduces the trapped molecules to the solution. When the trapped molecules are elements of reaction networks, their reversible trapping will constitute a way to control these networks remotely using light. The proposed system will be extended to include nanoparticles assembling in response to other colors of light (green, blue, etc.). The ESR will also work towards developing a novel light-responsive nanoparticle self-assembly system that will operate in aqueous environments.
Supervisor | Name : Prof. Rafal Klajn Email : rafal.klajn@weizmann.ac.il Website : https://www.weizmann.ac.il/Organic_Chemistry/Rafal/index.html |
Host Institution | Department of Organic Chemistry Weizmann Institute of Science 76100 Rehovot, Israel |
In this project, the ESR will use nanoscale surface-chemical patterns to control the local distribution and concentration of components (molecules or nanoparticles) of chemical reaction networks (CRNs). The goals are to induce directed local transport in supramolecular assemblies and to enrich highly diluted species at predetermined locations, both of which are essential for achieving sufficient concentrations to drive chemical reactions in predefined nanoscale compartments. In a collaboration with an academic partner (secondment), the ESR will exploit the localisation of antagonistic catalysts (reducing/oxidizing catalysts) in close proximity on a surface to induce molecular transport from one site to another mediated by the supramolecular structure. The nanoscale reactive surface patterns will be fabricated by thermal scanning probe lithography (t-SPL)[1], which produces functional areas that can be modified by standard coupling chemistries. During a further secondment, this technique will be used to sequentially pattern enzymes. Thus, we will fabricate complex geometries of antagonistic (e.g., reducing and oxidizing catalysts) or synergistic (e.g., enzyme / co-factor) surface areas. |
[1] Carroll, K. M.; Wolf, H.; Knoll, A. W.; Curtis, J. E.; Zhang, Y.; Marder, S. R.; Riedo, E.; Duerig, U. Langmuir 2016, 32, 13600-13610.
Supervisor | Name : Heiko Wolf Email : hwo@zurich.ibm.com Website : https://www.zurich.ibm.com/st/nanoscale/control.html |
Host Institution | IBM Research – Zurich IBM Research GmbH Säumerstrasse 4 8803 Rüschlikon, Switzerland |
Required profile | The candidate should hold a MS degree in Physics or Chemistry, ideally with a background in Local Probe Methods, Surface Chemistry, Physical Chemistry, and Soft Matter. Interest for interdisciplinary research is essential. Research stays are planned at TU Delft and University of Strasbourg. |
WORKPACKAGE 3: Materials based on CRNs
CRNs hold great promise for autonomous, dynamic and adaptive materials—beyond what state-of-the-art responsive materials can offer. This consortium has already pioneered several approaches to, e.g., encode hydrogels with tunable lifetimes.[1] Progress in this direction relies critically on finding advanced pathways for modulating internal and external feedback mechanisms to pre-orchestrate events in time and to find pathways to adaptation to outside signals. Additionally, biocompatible fuels are strongly needed to come to more benign systems and to be able to interface such autonomously dynamic and adaptive materials with the biological world. Advanced feedback systems beyond simple non-linear chemical activation and deactivation process included chemo-mechanical (or, more generally, structural) feedback mechanism, which have proven very difficult to implement. One example is a chemo-mechanochemical feedback system, where catalyst-bearing micro-posts heat up due to a chemical reaction and in response bend, which removes them from the reagent solution, thus stopping the heating process.[2] In another example, a pH-responsive hydrogel with the (proton-autoactivated) bromo-sulphite reaction was used.[3] The latter approach resulted in gel-oscillations in which the dynamics came from the feedback of the shape of the gel and internal pH gradients, and not just from the chemical dynamics. The (chemo)mechanochemical feedback is arguably the most complicated way to introduce instabilities in a CRN, but it can lead to more life-like properties of artificial biomaterials. The goal of WP3 is to systematically explore the coupling of CRNs and materials, mainly by using self-assembled materials that can be controlled by a CRN, or by engineering feedback due to swelling / shrinking of responsive materials.
[1] Heinen, L.; Walther, A. Soft Matter 2015, 11, 7857.
[2] He, X. et al., Nature 2012, 487, 214-218.
[3] Horváth, J., Szalai, I., Boissonade, J. & Kepper, P. D. Soft Matter 2011, 7, 8462-8472.
A highly promising way to achieve supramolecular feedback is to bring CRN under catalytic control, in which activation or deactivation of the catalysts by the CRN leads to the desired positive or negative feedback, respectively. In this project we will develop a generic approach for reversible feedback control of CRNs without the need for catalyst replenishment by controlling the accessibility or activity of the catalysts by their supramolecular environment. We will achieve feedback control of a CRN by developing a simple CRN that produces a self-assembling system, which upon self-assembly triggers the forward or backward catalyst activity. In this project we will first design and synthesise a simple CRN based on nicotinamide based self-assembling building blocks, which can be cycled between the oxidised, positively charged and hence non-assembling state and the reduced, non-ionic and hence self-assembling state by a rhodium-catalysed reduction and a flavin or metal porphyrin-catalysed oxidation reaction. We will then explore the coupling of self-assembly and CRN activity, investigate the boundary conditions for positive and negative feedback, and finally explore how mesophase formation and viscoelastic properties can be controlled by operation of the CRN. During secondments we will explore how mesophase structure can be controlled by surface-confined CRN catalysts, and we will explore possible theoretical models to analyse how energy dissipation and mesophase formation are related.
Supervisor | Name : prof. dr. Jan H. van Esch Email : j.h.vanesch@tudelft.nl Website : |
Host Institution | Department of Chemical Engineering |
Required profile | You have a strong background in supramolecular chemistry, polymer chemistry and/or physical chemistry. You have the ability to synthesize organic compounds and/or polymers, and perform kinetic and/or equilibrium studies. Desirable experience includes (a) NMR, HPLC, GPC, MS (b) microscopy (c) kinetics (d) rheology. It is essential that you are able to demonstrate competence in these areas, as judged by publications (or papers in press) in high quality peer reviewed journals or an MSc Thesis on a relevant topic. Very good spoken and written English is mandatory. |
Nanostructures formed by self-assembly of organic molecules (e.g. dyes, amphiphiles, gelators) are often dictated by thermodynamics, while their responsiveness is ruled by the height of energy barriers between the energy minima. By coupling self-assembly to a CRN, stability and dynamics can be decoupled, leading to materials that can be (mechanically) strong, but can still be remodelled if needed. Here, we propose to prepare supramolecular materials whose assembly can be controlled by phosphorylation/dephosphorylation processes, leading to non-equilibrium materials with more life-like properties. We base our design on peptide derivatives of benzene-1,3,5-tricarboxamide M whose assembly can be controlled by enzymatic phosphorylation–dephosphorylation cycles of a serine residue (i.e., phosphorylation leads to highly charged molecules M* that will repel and disassemble, see the Figure). The interactions of the enzymes with the assembled species will be studied at NANOT using their microscale thermophoresis technology. In addition, a secondment to ALU-FR will be done to see if this approach can be used to develop time-programmable materials (as they have shown previously).
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The next generations of soft materials will feature unprecedented dynamic, adaptive and interactive properties beyond the rather static properties we know so far. The key to empower such materials with such features is to install feedback loop and provide them with fuel to become active by translating the chemical fuel into work. You, as ESR, will engage in the design of stimuli-responsive polymeric materials that will be coupled with pH feedback mechanisms to make innovations in the field of transient and dynamic materials with programmable lifetimes. The focus will be set on materials presenting unusual mechanical properties, such as programmable strain stiffening hydrogels to mimic biological tissues, or for the use in soft robotics, as well as on photonic materials that can give rise to lasers. You will learn on a synthetic side to master advanced polymer chemistry tools to tailor polymer architectures (in particular controlled radical polymerization techniques) and you will also learn how to make transient pH profiles using pH modulating enzymatic reactions. A combination with 3D printing will allow you to design actuators for soft robotics. On an analytical side, you will become an expert in polymer science, in mechanical properties of hydrogels, optical properties of photonic materials, and in electron microscopic techniques. The project is strongly interdisciplinary and connects polymer science with systems chemistry and materials applications in hydrogels, soft robotics, and photonic. Two international secondments to CREANET partners, one to an academic and one to industrial partner, are foreseen in the framework of this project. Selected recent references on the topic: 1. “Materials Learning from Life: Concepts for Active, Adaptive and Autonomous Molecular Systems” Chem. Soc. Rev. 46, 5588 (2017). 2. “Biocatalytic Feedback-Driven Temporal Programming of Self-Regulating Non-Equilibrium Peptide Hydrogels” Angew. Chem. Int. Ed, 54, 13258 (2015). 3. “Photonic devices out of equilibrium: transient memory, signal propagation and sensing” Adv. Mater. 29, 1521 (2017) 4. “Antagonistic Enzymes in a Biocatalytic pH Feedback System Program Autonomous DNA Hydrogel Life Cycles” Nano Lett. 17, 4989 (2017). |
5. “Modular Design of Programmable Mechanofluorescent DNA Hydrogels” Nature Commun. 10, 529 (2019).
Supervisor | Name: Prof. Dr. Andreas Walther Email: andreas.walther@makro.uni-freiburg.de Website: www.walther-group.com |
Host Institution | Institute for Macromolecular Chemistry, University of Freiburg, Germany. |
Required profile | As an ideal candidate you are creative, highly self-motivated, ambitious and communicative, and have obtained a M.Sc. degree in chemistry or a closely related discipline. A previous knowledge and hands-on expertise polymer synthesis, polymer materials or molecular systems is highly desirable. We stand ready to teach you more! A keen interest in the combination of fundamental sciences with applications, advanced analytics (in particular microscopy) and the will to work in an interdisciplinary and multinational program is an important prerequisite. |
Using catalysis, certain reaction pathways in CRN-based active materials can be biased, changing the behavior of these active materials. When a catalyst is applied that changes activity in response to an external chemical or physical signal or location in space, the active material becomes responsive to signals from its environment. These concepts will be used to interface CRN-based active materials with biological processes, or on the other hand to use damage in polymer materials as a signal to invoke the self-healing properties of active materials. In the current project, we will use chemical signals arising from damage in polymer materials as a trigger to make an active material self-healing. Our goal is to couple the CRN-based active material to mechanical events by biasing a certain reaction pathway in the CRN using a catalyst, that responds to the mechanically generated signal. As such, these mechanisms are quite reminiscent of the signal transduction pathways found in living organisms, which also rely on signal-induced catalyst activation. Specifically, we will develop (i) protected catalysts that can be deprotected and activated using chemical signals derived from processes occurring in the material, and ii) CRN activation leading to transient catalyst activation, in turn leading to an amplified materials response. The self-healing behavior, mechanism and application will be investigated together with and through secondments with industrial and academic partners in the Creanet consortium.
Supervisor | Name : Dr. Rienk Eelkema Email : r.eelkema@tudelft.nl Website : tudelft.nl/cheme/eelkema |
Host Institution | Department of Chemical Engineering, Delft University of Technology Delft, the Netherlands |
Required profile | You have a strong background in synthetic organic chemistry, supramolecular chemistry and/or polymer chemistry. You must have practical skills in multi-step organic synthesis including the ability to select and execute appropriate purification techniques for isolating compounds. Experience in polymer synthesis and characterization, and spectroscopic measurements is highly advantageous. Desirable experience includes (a) NMR, HPLC, GPC, MS (b) microscopy (c) kinetics (d) rheology. It is essential that you are able to demonstrate competence in these areas, as judged by publications (or papers in press) in high quality peer reviewed journals or an MSc Thesis on a relevant topic. Very good spoken and written English is mandatory. |
Several dissipative self-assembly systems based on nanoparticles have been developed, but they are all limited to organic (typically hydrophobic) solvents. In order to interface them with biological systems, however, such dynamically self-assembling nanoparticles have to operate in water. In this project, the ESR will develop a range of nanoparticle-based systems compatible with aqueous environments. Various biocompatible small-molecule compounds (such as guanosine triphosphate; GTP) will be used as chemical fuels driving dissipative self-assembly. Detailed understanding of the dynamics of formation and destruction of these materials will be achieved using a variety of experimental techniques, including surface probe microscopies, advanced optical tracking, as well as electron microscopy, including in-situ / liquid cell setups. The long-term goal of this project is to carry out dissipative self-assembly of nanoparticles inside living organisms.
Supervisor | Name : Prof. Rafal Klajn Email : rafal.klajn@weizmann.ac.il Website : https://www.weizmann.ac.il/Organic_Chemistry/Rafal/index.html |
Host Institution | Department of Organic Chemistry Weizmann Institute of Science 76100 Rehovot, Israel
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