RESEARCH OPPORTUNITIES / EXTEND YOUR KNOWLEGE & SUPPORT YOUR PRACTICE / RESEARCH OPPORTUNITIES / EXTEND YOUR KNOWLEGE & SUPPORT YOUR PRACTICE /
Title:
EXPLORING PROTEIN NANOCAGES FUNCTIONAL AND STRUCTURAL CHARACTERISTICS
Objectives:
Advanced protein nanocages (ferritins and encapsulins) structural and functional characterization leading to bioengineered macromolecules with fine-tuned stability, molecular interactions and encapsulating/carrier properties. Development of biocompatible nanocages capable of encapsulating heterometallic biomineral cores, small molecules and proteins/enzymes, particularly suitable to enhance cancer therapy.
Enrolment:
Degree in Radiation Biology and Biophysics, Universidade NOVA de Lisboa
Other Institutions Involved:
Universität Potsdam | CNRS | Queen's University Belfast
Contact: ︎︎︎ Alice S. Pereira or ︎︎︎ Pedro Tavares
Title:
MOLECULAR REDUCTION BY ELECTRON TRANSFER
Objectives:
Using a crossed molecular beam technique, electron transfer processes will be investigated in collisions of fast neutral radicals and potassium atoms with neutral molecular targets. Formation of negative ions will be investigated. These experiments will clarify the main differences between molecules undergoing such electron transfer processes and those from single free electron attachment experiments in terms of their major reaction products and molecular underlying mechanisms. Seminal work on hydrated clusters.
Enrolment: Degree in Radiation Biology and Biophysics, Universidade NOVA de Lisboa
Other Institutions Involved:
Siedlce University of Natural Sciences and Humanities | Universität Innsbruck, Consejo Superior de Investigaciones Científicas (Madrid) | Open University | ︎︎︎ IONICON
Contact:
︎︎︎ Paulo Limão Vieira
Title:
INDUCED MOLECULAR DISSOCIATION BY ELECTRON COLLISIONS WITH CONDENSED MOLECULES AND ITS RADIOBIOLOGICAL IMPLICATIONS
Objectives:
Biologically relevant molecules/macromolecules and molecular radiosensitizers condensed on metallic and graphene substrates will be irradiated with low and high energy electron beams, in order to characterise the induced molecular damage in terms of bond breaking and molecular dissociations. Molecular dissociation on metal and graphene surfaces will be calculated from the numerical solution of the time-dependent Schrödinger equation by using a realistic potential obtained from density functional theory calculations together with ab initio Born-Oppenheimer molecular dynamics calculations. Experiments and theory will provide a realistic interpretation on the molecular processes underpinning radiation damage, and will be compared with the observed biological effects when living cells are irradiated with clinical electron beams.
Enrolment:
Degree in Radiation Biology and Biophysics, Universidade NOVA de Lisboa
Other Institutions Involved:
Open University | Siedlce University of Natural Sciences and Humanities | ︎︎︎ Université de Sherbrooke
Contact:
︎︎︎ Pedro Tavares or ︎︎︎ Gustavo García
Title:
RADIOBIOLOGICAL MODELS FOR CHARGED PARTICLE BEAM RADIOTHERAPY TECHNIQUES USING MOLECULAR RADIOSENSITIZERS
Objectives:
Collisional data for electron, proton and heavy ion interactions with molecular radiosensitizers will be analysed and compiled into databases. These data will be used to feed an event-by-event Monte Carlo simulation program able to provide the induced molecular damage in terms of energy deposition and induced molecular dissociations. Using additional data for water molecules, DNA and RNA bases the tracks of primary and secondary particles, with and without the presence of molecular radiosensitizers, will be simulated in order to evaluate the induced molecular damage. Produced biological damage will be evaluated by irradiating cancerous epithelial cells with electron and proton beams in preclinical situations. The correlation between the simulated molecular damage and the observed biological effect will allow to develop a treatment planner for electron beam intraoperative radiotherapy, proton therapy and carbon ion therapy.
Enrolment:
Universidad Autónoma de Madrid
Other Institutions Involved:
FCT NOVA | Universität Innsbruck | Siedlce University of Natural Sciences and Humanities | Universität Potsdam
Contact:
︎︎︎ Gustavo García
Title:
SPATIAL AND TEMPORAL MODULATION OF RADIATION EXPOSURE AND THE ROLE OF MOLECULAR RADIOSENSITISERS
Objectives:
Advanced radiotherapies are evolving from the delivery of uniform exposures to the tumour to spatially heterogeneous treatments including different types of grids, micro, and mini-beams. These can offer enhanced tumour cell killing whilst reducing the damage to surrounding normal tissues. In parallel, it is becoming clear that there may be significant advantages with the delivery of high dose-rate exposures in contrast to those currently used clinically. This is being tested not only for high energy X-ray beams but also other radiation types including protons. The optimal delivery of these beams and the interaction between different spatial and temporal delivery patterns is not well defined radiobiologically. There is a need to determine the role of different spatial and temporal patterns in radioresistant cancer models. Molecular radiosensitizing agents are available in a range of different formats, including nano-formulations and can offer enhanced effects in tumour models. However, the interaction between these molecular agents and spatial and temporal modulation is not known. This project will test a range of spatial and temporally distinct kilovoltage X-ray beams in their effectiveness to cause DNA damage and inactivate radioresistant brain lung and prostate cancer models.
Enrolment:
Queen’s University Belfast
Other Institutions Involved:
FCT NOVA | CSIC
Contact:
︎︎︎ Kevin M. Prise
Title:
UNDERSTANDING CLUSTERING EFFECTS ON LOW-ENERGY ELECTRON ATTACHMENT TO RADIOSENSITIZERS
Objectives:
As the most abundant products of ionizing radiation, low-energy electrons play a critical role in biological radiation damage, notably through dissociative electron attachment (DEA). The use of radiosensitizers to enhance targeted radiation damage (increasing the therapeutic ratio) is a key area of development in radiotherapy. However, while several groups have recently studied DEA to isolated radiosensitizer molecules, the effects of the condensed environment on low-energy electron attachment to these molecules have not been studied to date. This project will combine experiments and theory at the OU: i) DEA experiments on radiosensitizers in the gas phase and in hydrated clusters: the objective is to characterise the effect of hydration on the interaction between low energy electrons and the radiosensitizer; ii) Electron scattering calculations on isolated radiosensitizers and on radiosensitizers clustered with a single water molecule: the objective is to identify and characterise the resonances that lead to DEA and how the hydration environment modifies them.
Enrolment:
Degree in Physical Sciences, Open University
Other Institutions Involved:
Universität Potsdam | CSIC
Contact:
︎︎︎ Jimena Gorefinkel or ︎︎︎ Sam Eden
Title:
LOW-ENERGY ELECTRON INTERACTION WITH POTENTIAL RADIOSENSITISERS
Objectives:
In order to investigate electron-induced reactions in radiosensitizers during the early stage of radiation damage, micro hydrated radiosensitizers will be formed by supersonic expansion and look for the formation of charged and neutral radicals upon electron ionisation and electron attachment (EA) by mass spectrometry. Electron beams with adjustable energy will be employed to monitor anion generation as a function of the initial electron energy. This will elucidate non-dissociative and dissociative EA channels by mass spectrometry together with cation formation as well. For example, as a possible molecular target for low-energy electrons, microhydrated tirapazamine will be generated to test hypotheses about radical formation from the negative ion. In addition, studies of small molecular systems containing Hf could be studied to gain fundamental knowledge about electron interaction with Hf nanoparticles suggested as radiosensitizers in radiation therapy.
Enrolment:
PhD in Physics, University of Innsbruck
Other Institutions Involved:
FCT NOVA | Universität Potsdam | ︎︎︎ IONICON
Contact:
︎︎︎ Stephan Denifl
Title:
LOW-ENERGY ELECTRON INTERACTION WITH POTENTIAL RADIOSENSITISERS
Objectives:
In order to investigate electron-induced reactions in radiosensitizers during the early stage of radiation damage, micro hydrated radiosensitizers will be formed by supersonic expansion and look for the formation of charged and neutral radicals upon electron ionisation and electron attachment (EA) by mass spectrometry. Electron beams with adjustable energy will be employed to monitor anion generation as a function of the initial electron energy. This will elucidate non-dissociative and dissociative EA channels by mass spectrometry together with cation formation as well. For example, as a possible molecular target for low-energy electrons, microhydrated tirapazamine will be generated to test hypotheses about radical formation from the negative ion. In addition, studies of small molecular systems containing Hf could be studied to gain fundamental knowledge about electron interaction with Hf nanoparticles suggested as radiosensitizers in radiation therapy.
Enrolment:
PhD in Physics, University of Innsbruck
Other Institutions Involved:
FCT NOVA | Universität Potsdam | ︎︎︎ IONICON
Contact:
︎︎︎ Stephan Denifl
Title:
STUDIES OF THE MECHANISMS OF RADIOSENSITIZATION AT THE MOLECULAR LEVEL
Objectives:
The investigation of collisions between electrons and biomolecules and molecular radiosensitizers in the gas phase. The primary objectives are: Identification of the fragment ions which are formed from electron attachment/ionisation to gas phase biomolecules. Selective bond cleavage by electron induced dissociation. Cross section measurements for electron capture/ionisation processes under single collision conditions. Investigation of the kinetics and mechanism of electron capture processes under high pressure environments. Objectives will be achieved by utilising electron-molecular crossed beam technique, GC-ECD, and swarm technique.
Enrolment:
PhD in Chemistry, Siedlce University
Other Institutions Involved:
FCT NOVA | Universität Potsdam
Contact:
︎︎︎ Janina Kopyra
Title:
QUANTIFICATION OF DNA RADIATION DAMAGE BY DNA NANOTECHNOLOGY
Objectives:
DNA origami nanostructures allow for an absolute quantification of DNA radiation damage in well-defined DNA sequences (single-stranded, double-stranded as well as DNA that is modified with radiosensitizers). Such DNA targets modified with novel radiosensitizers will be irradiated with low-energy electrons in the range. This will be done with DNA in two different hydration states, i.e. with crystal water still present and fully lyophilized. Additionally, the DNA origami nanostructures will be modified with Hf nanoparticles as well as mineral containing proteins to study the effect of the presence of these entities on radiation induced DNA damage in their surroundings.
Enrolment:
Universität Potsdam
Other Institutions Involved:
Siedlce University of Natural Sciences and Humanities | FCT NOVA | Open University | CSIC
Contact:
︎︎︎ Ilko Bald
Title:
IRON-SULFUR CENTER HOMEOSTASIS: BIOGENESIS, STORAGE AND ROLE IN OXIDATIVE STRESS RESISTANCE
Objectives:
Iron-sulfur clusters (FeS) are protein cofactors involved in a multitude of cellular processes including electron transfer, enzyme catalysis, sensing and gene regulation. Due to their essential role, any defect in their biosynthesis leads to severe diseases. In addition, their inherent structural plasticity and redox sensitivity facilitate the regulation of gene expression through protein conformation changes and constitute an essential process in sensing and resistance to oxidative stress related to radiation damages, microbial infections or cancer. Understanding FeS cluster structural conversions at the molecular level is a great challenge and remains elusive in most cases. By using EPR spectroscopy techniques together with other spectroscopies (CD, Resonance Raman, Mössbauer), the aim of this project is to decipher the critical steps of the FeS cluster transformations in the FeS biosynthesis pathway in mammals (ISC machinery) and in proteins involved in cellular regulation processes in response to oxidative stress.
Enrolment:
PhD in Chemistry, CNRS (Aix-Marseille University)
Other Institutions Involved:
FCT NOVA | Universität Potsdam
Contact:
︎︎︎ Bruno Guigliarelli
Other Opportunities: