Grant: Discovery Grants Program - Individual
Université de Sherbrooke
$64,000.00
Low-energy electron induced processes in radiation damage: relationship to astrochemistry, radiobiology and radiotherapy
EF 2020-21
Résumé
Secondary electrons are the most abundant species produced by high-energy radiation in matter; most have energies below 20 eV. Such low-energy electrons (LEEs) play key roles in a range of fields, including astrochemistry, photochemistry and radiation therapy. To understand and/or control of such phenomena, data is needed on LEE-induced processes occuring within, and at the interfaces of, molecular and biomolecular materials. Our objective during the next five years is to study LEE related phenomena in two distinct scientifically significant areas:
i) LEE induced damage to DNA and DNA complexes (DNAC, formed by binding potential or clinically-available radiosensitizers or chemotherapeutic agents to DNA): We will characterize the fundamental mechanisms of LEE interactions in DNA and DNAC in targets of increasing complexity (e.g., films of DNA subunits, oligonucleotides, plasmid DNA, etc.,) under experimental conditions that progressively approach those encountered in cells. This will be done by coadsorbing in these films O2, H2O, amino acids and mixtures thereof, under ultrahigh vacuum (UHV) or at atmospheric pressure. Thus, this research seeks an improved understanding of LEE-induced processes in DNA and DNAC in close contact with cellular molecules. To achieve this goal, we will continue to develop state-of-the-art bimolecular thin-film technology and new LEE sources. Since DNA is the target in radiotherapy, this work will help identify new modalities and molecular agents to improve cancer treatment with radiotherapy alone or combined with chemotherapy. Previous research on these fundamental aspects of LEE-induced radiation damage to biomolecules was supported by the CIHR, but presently CIHR funding is more appropriately requested only for the clinical applications of such work.
ii) Astrochemistry: radiation processing of molecular ices, like to those found in space environments is of considerable current interest for the interpretation of astronomical data and the synthesis of complex molecules. The chemistry initiated by LEEs in such ices may thus relates to the formation of pre-biotic molecules by cosmic and UV irradiation and the origins of life. We will continue our studies into LEE-driven chemistry on thin-film ices formed in UHV. These will contain mixtures of molecules such as H2O, NH3, CO2, CO and CH4 that condense upon dust grains in the interstellar medium and are present in comets and planetary ices. Building on our recent work on the identification of glycine in LEE-irradiated ices, we will attempt to investigate the formation of other amino acids, small peptides, DNA bases and related molecules.
In both areas, we will focus on the identification of basic physical mechanisms that dominate product yields, including transient anion formation. This research is intended to promote the highest levels of research quality in the field of LEE-molecule interactions, spur academic interest and provide a stimulating training environment.
Programme
Discovery Grants Program - Individual
Bénéficiaire
Emplacement
Quebec, Canada
Type de bénéficiaire
Academia
Type
Grant
Source
NSERC's Awards Data
Tel que publié
Application id
RGPIN-2019-05825
Name nom
Sanche, Léon
Department département
Médecine nucléaire et radiobiologie
Organization id
68
Institution établissement
Université de Sherbrooke
Province en
Québec
Province fr
Québec
Country en
CANADA
Country fr
CANADA
Fiscal year exercice financier
2020
Competition year année de concours
2019
Award amount
64000
Program id
RGPIN
Program name en
Discovery Grants Program - Individual
Program name fr
Programme de subventions à la découverte - individuelles
Group en
Discovery grants programs
Group fr
Programmes de subventions à la découverte
Committee code
1504
Committee name en
Chemistry
Committee name fr
Chimie
Area of application code
1200
Area of application group en
Advancement of knowledge
Area of application group fr
Avancement des connaissances
Area of application en
Advancement of knowledge
Area of application fr
Avancement des connaissances
Research subject code
3402
Research subject group en
Physical chemistry
Research subject group fr
Chimie physique
Research subject en
Surface and interfacial chemistry
Research subject fr
Chimie des surfaces et des interfaces
Installment
inst:2-5
Partie
4
Nb partie
5
Application title
Low-energy electron induced processes in radiation damage: relationship to astrochemistry, radiobiology and radiotherapy
Keyword
NSERC
Application summary
Secondary electrons are the most abundant species produced by high-energy radiation in matter; most have energies below 20 eV. Such low-energy electrons (LEEs) play key roles in a range of fields, including astrochemistry, photochemistry and radiation therapy. To understand and/or control of such phenomena, data is needed on LEE-induced processes occuring within, and at the interfaces of, molecular and biomolecular materials. Our objective during the next five years is to study LEE related phenomena in two distinct scientifically significant areas:
i) LEE induced damage to DNA and DNA complexes (DNAC, formed by binding potential or clinically-available radiosensitizers or chemotherapeutic agents to DNA): We will characterize the fundamental mechanisms of LEE interactions in DNA and DNAC in targets of increasing complexity (e.g., films of DNA subunits, oligonucleotides, plasmid DNA, etc.,) under experimental conditions that progressively approach those encountered in cells. This will be done by coadsorbing in these films O2, H2O, amino acids and mixtures thereof, under ultrahigh vacuum (UHV) or at atmospheric pressure. Thus, this research seeks an improved understanding of LEE-induced processes in DNA and DNAC in close contact with cellular molecules. To achieve this goal, we will continue to develop state-of-the-art bimolecular thin-film technology and new LEE sources. Since DNA is the target in radiotherapy, this work will help identify new modalities and molecular agents to improve cancer treatment with radiotherapy alone or combined with chemotherapy. Previous research on these fundamental aspects of LEE-induced radiation damage to biomolecules was supported by the CIHR, but presently CIHR funding is more appropriately requested only for the clinical applications of such work.
ii) Astrochemistry: radiation processing of molecular ices, like to those found in space environments is of considerable current interest for the interpretation of astronomical data and the synthesis of complex molecules. The chemistry initiated by LEEs in such ices may thus relates to the formation of pre-biotic molecules by cosmic and UV irradiation and the origins of life. We will continue our studies into LEE-driven chemistry on thin-film ices formed in UHV. These will contain mixtures of molecules such as H2O, NH3, CO2, CO and CH4 that condense upon dust grains in the interstellar medium and are present in comets and planetary ices. Building on our recent work on the identification of glycine in LEE-irradiated ices, we will attempt to investigate the formation of other amino acids, small peptides, DNA bases and related molecules.
In both areas, we will focus on the identification of basic physical mechanisms that dominate product yields, including transient anion formation. This research is intended to promote the highest levels of research quality in the field of LEE-molecule interactions, spur academic interest and provide a stimulating training environment.