1 / 70

September 2014 : 13 PhD positions in different fields :

EU PhD training : Marie Curie ITN ARGENT Advanced Radiotherapy, Generated by Exploiting Nanoprocesses and Technologies. Univ Paris Sud-Orsay (FR) Open university (UK) Queens university Belfast (UK) Univ of Caen (FR) Univ of Frankfurt FIAS (D) Univ Madrid (S) GSI (Darmstadt, D)

ronnie
Download Presentation

September 2014 : 13 PhD positions in different fields :

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript

  1. EU PhD training : Marie Curie ITN ARGENT Advanced Radiotherapy, Generated by Exploiting Nanoprocesses and Technologies Univ Paris Sud-Orsay (FR) Open university (UK) Queens university Belfast (UK) Univ of Caen (FR) Univ of Frankfurt FIAS (D) Univ Madrid (S) GSI (Darmstadt, D) NanoH, SME (FR) ChemaTech( SME, FR) Quantumwise( SME, Danemrk) • September 2014 : • 13 PhD positions in differentfields : • Chemistry : synthesis, functionalization of NP • Physics / chemicalphysics (experimental/theory) • Medicalphysics/radiation physics • Biology (radiation) Contact : sandrine.lacombe@u-psud.fr

  2. RESEARCH • Improvement of the hadrontherapy protocols using nanosensitizers (S. LacombeOrsay) • Uptake dynamics of nanoagents and effect on radioenhancement (Orsay/Belfast) • Development of new modules for ATK code for modelling radiosensitizingnanoagents (A. Solovyov/industrialin Danemark) • Bond-breaking as a descriptor for nanodosimetry (G. Garcia-Madrid) • Validation of models in medical radiation planning (G. Garcia, Madrid) • Nanoagent functionalization aiming at tumor targeting and biocompatibility (industrial in France) • Nanoscale understanding of cell signalling and biological response (K.Prise, Belfast) • Multiscale understanding of radiation biodamage (A. Solovyov, Frankfurt and F. Curell, Belfast) • Development of Lanthanides based nanosensitizers for theranostic ((industrial in France) • Molecular efficiency of radiosensitizers in ion-induced radiation damage processes (B. Huber, Caen) • OER prediction on the nanoscale for a target tissue in different conditions of irradiation and oxygenation (E. Scifoni, M. Durante, Darmstadt) • Exploring site specificity, structure and sequence dependence of radiation-induced damage (N. Mason, Milton Keynes) • Impact of nanoscale processes and agents on biodamage complexity in the presence of nanoagents(A. Solovyov, Frankfurt) Contact : sandrine.lacombe@u-psud.fr

  3. RESEARCH • Improvement of the hadrontherapy protocols using nanosensitizers (S. LacombeOrsay) • Uptake dynamics of nanoagents and effect on radioenhancement (Orsay/Belfast) • Development of new modules for ATK code for modelling radiosensitizingnanoagents (A. Solovyov/industrialin Danemark) • Bond-breaking as a descriptor for nanodosimetry (G. Garcia-Madrid) • Validation of models in medical radiation planning (G. Garcia, Madrid) • Nanoagent functionalization aiming at tumor targeting and biocompatibility (industrial in France) • Nanoscale understanding of cell signalling and biological response (K.Prise, Belfast) • Multiscale understanding of radiation biodamage (A. Solovyov, Frankfurt and F. Curell, Belfast) • Development of Lanthanides based nanosensitizers for theranostic ((industrial in France) • Molecular efficiency of radiosensitizers in ion-induced radiation damage processes (B. Huber, Caen) • OER prediction on the nanoscale for a target tissue in different conditions of irradiation and oxygenation (E. Scifoni, M. Durante, Darmstadt) • Exploring site specificity, structure and sequence dependence of radiation-induced damage (N. Mason, Milton Keynes) • Impact of nanoscale processes and agents on biodamage complexity in the presence of nanoagents(A. Solovyov, Frankfurt) SCIENTIFIC AND SOFT SKILLS: 3 monthstutorials+ soft skills (MBA 3 weeks) + 1 monthindustrial site Contact : sandrine.lacombe@u-psud.fr

  4. A roadmap for Europe’s research on radiation damage NANO - IBCT Sopot May 20 - 24 2013 Nigel Mason The Open University

  5. A history How did we get to be in SOPOT ? Question (for academics) How many people did you know in this room in 2003 ?

  6. Question for atomic molecular and electron collisions people In 2003 what did you know about DNA ? Cells and radiotherapy ? RBE ? LET ? (Nano) dosimetry What molecular targets were you studying ? ECAMP 2004 only 9/850 papers on biomolecules ! >20 on N2 and >100 on rare gases

  7. Question for biological and clinical people In 2003 had you heard of DEA ? Anions and Resonances ? Did you know about experimental EU ion beam facilities (GANIL, Groningen ? Had you visited one ?

  8. The conjecture There has been a big change in what we study and why ! A new (trans disciplinary) EU community has developed. It has been useful, successful and

  9. The conjecture There has been a big change in what we study and why ! A new (trans disciplinary) EU community has developed. It has been useful, successful and FUN

  10. Where is all began (for many of us!) • The pioneering work of Sanche et al and the (in)famous Science paper • Resonant Formation of DNA Strand Breaks by Low-Energy (3 to 20eV) Electrons. Science 287, 1658-1660 (2000). B. Boudaiffa, P. Cloutier, D. Hunting, M.A. Huels et L. Sanche.

  11. Strand breaks of DNA SSB 10 DSB 10 DNA breaks per 104 incident electrons 5 e- + DNA → DNA-* → fragments 0 0 5 10 15 20 Electron Energy (eV) L. Sanche et al. Science, 287 (2000) 1659 and PRL (2004)

  12. These ‘fundamental’ studies coincided with new therapies e.g. carbon ion therapy. (Nano-IBCT)

  13. Hence The idea/development of need to bring two disparate communities together Atomic, molecular physics/ physical chemistry And Radiation chemists/medical physics

  14. This research has been developed through networks

  15. RADAM first COST Action Presented 2002 WARSAW Started 2003 RADAM 1 Lyons 2004

  16. RADAM Meetings 1 2004 Lyons (food) 2 2005 Potsdam ( a tutorial) 3 2006 Groningen (Euro football!) 4 2007 Dublin (rain!) 5 2008 Debrecen (thunder!) 6 2009 Frankfurt 7 2010 Madrid Then IBCT Nano Caen 2011 and Sopot 2013

  17. The exchanges RADAM; ECCL; EIPAM & Nano-IBCT has supported Over 450 visits/exchanges !! They have built the community

  18. So what have we learnt ? DNA damage (key process) needs trans disciplinary research Lets look at interconnections in ‘RADAM’ community

  19. To understanding DNA Damage (Solov’yov) Energy loss by the incident particle Bragg peak, its position, shape, and height Energy spectrum, number density, plasma Production of secondary electrons, holes Propagation in a dense medium Heating of the medium Excitation of the medium SSB’s and DSB’s Production of Free Radicals Damage of the DNA Solov’yov et al., Phys. Rev. E, v.79, p. 011909-(1-7) (2009) Europhysicsnews, v.40, n.2, p.21-24 (2009) 22 August 2014

  20. Or view of Werner Friedland physical track structurecalculation pre-chemical and chemical stagecalculation DNA target modelling biological effect simulation

  21. … has to be complemented by target structure simulation … where damage to DNA in the nucleus is - supposed to be - the main initiating event by which radiation causes long-term harm to organs and tissues of the body after low doses of radiation Biological effectsimulationsusingtrackstructures Track structure simulation … based on cross sections for interactions of primary and secondary ionising particles (electrons, photons, protons, alphas, ions) … and by radiation effect simulation where double-strand breaks (DSB) in genomic DNA are – supposed to be -crucial initial lesions for causing critical damage after irradiation

  22. Where are we now ? • Our studies in the mechanisms of radiation damage has developed rapidly in the last decade. • There has been a lot of work on the fragmentation (and hence stability) of biomolecules • In particular DEA (>80% of molecular targets for which DEA has been explored are biomolecules and studied since 2002 !)

  23. Bond Selectivity using Electrons Process of Dissociative Electron Attachment

  24. DEA Is a universal process Often simple H abstraction (M-H)- and is bond specific !

  25. DEA to biomolecules typical results -- Ptasinska DEA to biomolecules typical results -- S → C5H6N2O2- electron attachment → (T-H)- + H → (T-2H)- + neutral(s) → C4H5N2O-+ neutral(s) → C2H3N2O- +neutral(s) → C3H2NO- +neutral(s) → C3H4N- +neutral(s) → OCN- +neutral(s) → CN- +neutral(s) → O- +neutral(s) → H- +neutral(s) dissociative electron attachment Thymine + e- → TNI-* 126 amu 125 amu 124 amu 99 amu 73 amu 68 amu 54 amu 42 amu 26 amu e- 16 amu 1 amu

  26. DEA in Thymine (M-H)- 125 amu 12 e- 10 8 Cross section (10-20 m2) 6 4 2 H loss 0 0 1 2 3 4 Electron energy (eV)

  27. DEA But what is real relevance to the cell biology ? Does it hold in condensed phase ? Can it explain any radiobiology phenomena ? (e.gradiosensitizers)

  28. Desorption of anions and neutrals from Tetrahydrofuran

  29. Uracil Thymine Bromouracil (Radiosensitizer)

  30. Freie University Berlin s ≈ 600 Å2 + Br.

  31. Ion impact Similar story to electrons/DEA Great progress in number of systems studied and exploration of fragmentation Stability - necleobases more stable than sugars (e.g. uracil cfdeoxyribose) (Hoekstra)

  32. Groningen University • Ion irradiation of biomolecules • Eg C+ on nucleobases Deoxyribose and amino acids • Different fragmentation patterns

  33. Ion impact But …. Can this be extrapolated to cellular conditions and condensed phase ?) What is relevance of heavy ions (> Carbon ?)

  34. Photon impact Photostability Electronic state structure of biomolecules Quantum chemistry advances (DFT)

  35. Three Grand Challenges of theunderpinning fundamental science • Moving from the isolated gas phase to the cellular environment • Extend study of damage to DNA to other macromolecules in the cell and cell itself • Developing models of such damage for use in therapy etc.

  36. Moving from the isolated gas phase to the cellular environment Developing cluster sources e.g. nucleobases and water (S Eden OU) Study spectroscopy Collision dynamics PDRA post on offer

  37. Developments in understanding of fundamental processes is used to develop better models Allowed new track models to be developed

  38. Track modelling 5 single tracks Auger Neutral dissociation Ionisation 2 keV electrons in H2OPressure: 200 Torr Excitation

  39. Such models need • Cross sections !!!! • Real numbers not just phenomenology !

  40. Planning a Database Data users in various application fields * fusion science * astrophysics * industrial plasmas * environmental physics * medical (radiotherapy) etc. Data providers * theory * experiment Data provided Data requested Data search for check Data requests Data provide Data needs Data search Data provide feedback Data centers data compilation data evaluation (important but not easy) dissemination and updating of database retrievable online database = easy to access, use, find data International A&M data center network IAEA, NIFS, A-PAN, KAERI, NIST, ORNL, GAPHIOR, VAMDC,

  41. Electron interactions data in H2OeMOL data review and validation project

  42. Summary of the Recommended dataon the electron collision cross section for H2OY. Itikawa and N.J.Mason, J. Phys. Chem. Ref. Data 34 (2005)1

  43. e-H2O integral cross section data (Courtesy of G Garcia) Total scattering (5%) Integral elastic and inelastic (10%) Ionisation (7%) Excitation (15%) Neutral dissociation (15%)

  44. But such complete data sets are rare For most biomolecules MOST cross sections are missing Some may be calculated – eg ionisation (Theory – Kim (BE) and Deutsch Maerk ) And compare well with experiments Or for total, elastic, some excitations Quantemol package (J Tennyson)

  45. So lots of data needed ! • How do we co-ordinate data collection ? • Where does the user find it ? • When collected how/where is it stored and ‘ratified’ ?

  46. VAMDC will provide a one stop scientific data e-infrastructure enabling easy access to A+M data www.vamdc.org • To include RADAM database from COST Nano-IBCT network

  47. But beyond this…. Need to remember the chemistry And biology ……..

  48. chemical stage physico-chemical physical stage Particle tracks during physico-chemical and chemical stage 10-15 – 10-12 s 10-12 – 10-6 s • relax • auto-ionize • dissociate • diffuse • react esub ,H2O+ A1B1, B1A1 Ryd, db reaction rate constants k diffusion coefficients D eaq, •OH, H•, H2 H3O+, OH- , H2O2 eaq + eaq + 2H2O → H2 + 2OH- eaq + •OH → OH- eaq + H• + H2O → H2 + OH- eaq + H3O+→ H• + H2O eaq + H2O2→ OH- + •OH •OH + •OH → H2O2 •OH + H• → H2O H• + H• → H2 H3O+ + OH- → 2H2O A1B1 → H2O + DE 35% H• + •OH 65% B1A1→ H2O+ DE 30% H3O+ + •OH + eaq 55% H2 + •OH + •OH 15% Ryd,db → H2O + DE 50% H3O+ + •OH + eaq 50% H2O+ + H2O → H3O+ + •OH 100%

  49. Radiation damage to DNA Damage of the genome in living cell by ionising radiation is about1/3 a direct and 2/3 an indirect processes.

  50. DNA damage signalling in bystander cells Burdak-Rothkamm and Prise, 2009

More Related