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Introduction to Radiation Biophysics (Sommersemester 2023)

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Die Vorlesung findet Mai bis Juli präsent statt, jeweils Dienstag und Donnerstag, 9-11 Uhr. Die Unterrichtssprache ist Englisch. Der Kurs kann sowohl im Bachelor- als auch im Masterstudium belegt werden. Die Klausur wird im Bachelor benotet; im Master bleibt sie unbenotet und kann in die mündliche Prüfung mitgenommen werden:

Die erste Vorlesung ist am Donnerstag, dem 20.4.2023, und muss aus organisatorischen Gründen vollständig online stattfinden. Hierzu steht eine Plattform online über HeiConf-Audimax zu Verfügung:

Zugang über https://audimax.heiconf.uni-heidelberg.de/4fnk-xtaa-9yry-c769

Zeit:  Dienstag und Donnerstag 9:15h bis 10:45h

Sie müssen sich nicht vorab anmelden.

 

Inhalt (Contents):

Lecture 1 + 2 : Introduction to Radiation Biophysics, historical context and major discoveries leading to the current state of knowledge, the fundamental questions of radiation biophysics

  • Introduction – Radiation biophysics and its topics in the historical context and in the context of the incredible "whirlwind" of Nobel Prizes
  • The discovery of X-Rays
  • Basic characteristics of electromagnetic radiation, basic characteristics of ionizing radiation, X-Ray tube, applications in medicine, some other applications
  • The discovery of natural radioactivity
  • The discovery of artificial radioactivity
  • The project Manhattan – on the way to the first atomic bomb and its (mis)use
  • First signs of radiation toxicity and benefits

 Lecture 3 + 4: Structure of matter,

  • The path to the interior of the atom and the atomic nucleus, atom composition and models,
  • Discovery of electrons atomic shell composition
  • Discovery of atom nucleus, protons and neutrons
  • The first “transmutations”
  • Strangeness of the quantum world
  • Matter and antimatter, exotic atoms and antiatoms
  • Basic definitions of nuclides, isotopes, isotones, isobars, mirror nuclei
  • Quarks
  • “ZOO” of elementary particles (basic elementary particle systematics); is there something smaller than electrons and quarks?

Lecture 5 + 6 : the principles of radioactivity, types and characteristics of particular ionizing radiation types

  • Four main forces (just a basic introduction and importance for radioactivity)
  • Models of the atom nucleus
  • Binding energy, the “valley of stability”. Different types of atom nucleus instability (radioactivity), magic and double-magic nuclei
  • Eight basic types of ionizing radiation, decay chain types
  • Radiation activity of atoms
  • Kinetics of atom nucleus decay by radiation, the physical decay half-time
  • Basic laws of radiation decays

 Lecture 7 + 8: the principles of radioactivity, types and characteristics of particular ionizing radiation types

  • Directly and indirectly ionizing radiation
  • Interactions of ionizing radiation with matter and biological systems
  • Sparsely and densely ionizing radiation, Bragg curves and implications for radiotherapy
  • The mystery of cell killing efficiency by ionizing radiation
  • Direct and indirect (water radiolysis) effect of ionizing radiation
  • Unique processes associated with the interaction of ionizing radiation with biological systems
  • General principles of cell response to radiation damage
  • Basic units and quantities describing sources of ionizing radiation, fields of ionizing radiation, energy transfer of radiation to matter, and biological effects of different types of ionizing radiation (absorbed dose vs. equivalent dose vs. effective dose)
  • Internal contamination and committed effective dose; biogenic radionuclides and critical organs
  • Effect of the dose rate
  • Dose response curves

 Lecture 9 + 10: Biological effects of ionizing radiation

  • Effects of ionizing radiation on humans – the first observations and the knowledge accumulation
  • The cell composition and critical targets for ionizing radiation
  • Radiation damage to proteins, lipids, RNAs and DNA
  • Direct and indirect (water radiolysis) effect of ionizing radiation from the point of view of biomolecule damage
  • Effects of UV radiation¨
  • Categorization of ionizing radiation effects to humans; deterministic vs. stochastic effects; early and late effects, somatic vs. genetic effects, etc.
  • Radiosensitivity of different organisms
  • Radiosensitivity of different cell types to deterministic effects of ionizing radiation
  • Acute Radiation Syndrome (ARS), ARS categories by the severity (hematological, gastrointestinal, and neurovascular form), its causes, clinical symptoms, treatment and prognosis
  • Individual radiosensitivity and variable radiosensitivity of tumors
  • Other examples of deterministic effects (radiation skin burn, pneumonia, cataract, infertility
  • Consequences of “Russian games” in Chernobyl for Russian soldiers, Ukraine and West Europe
  • Stochastic effects, general characteristics
  • Epidemiological studies on stochastic effects – Hiroshima and Nagasaki atomic bombing victims
  • Disasters in Chernobyl and  Fukushima, critical points, differences, and lessons for the future; consequences for the disaster liquidators and civil victims; contribution of these atomic power plant disasters to the radiation background; comparison of health risks arising from irradiation due to Chernobyl disaster and other general activities of men
  • Low dose effects, dose response curves according to the linear non-threshold model (LNT), linear model with threshold dose, hypersensitivity and hyposensitivity (hormesis effect)
  • Carcinogenesis; clonogenic expansion, chromothripsis, protooncogenes and tumor suppressors, oncogenes, solid tumors and leukemia after radiation exposure; dsDNA breaks as a claymore in origin and treatment of tumours.

 Lecture 11 + 12: Stochastic effects of ionizing radiation, DNA damage and repair, applications of ionizing radiation in medicine, examples of selective tumor cell radiosensitization and normal cell radioprotection,

  • Carcinogenesis II
  • Radiation damage to DNA at the molecular level – types of DNA radiation lesions, mutagenesis, characteristics of chromatin damage by low-LET and high-LET ionizing radiation for micro- and nano-biodosimetry, relative biological efficiency (RBE) as function of LET
  • Structure of the cell nucleus and chromatin in association with principal life processes, namely DNA repair: new views on induction and repair of double-strand DNA breaks - spatiotemporal aspects,
  • Chromosomes, human karyotype, chromosome- and chromatid-type aberrations (translocations, deletions, inversions), influence of LET on the character of chromatin damage
  • (bio)dosimetry for nuclear accidents
  • Cell cycle and its relationship with cell radiosensitivity, DNA repair and carcinogenesis; DNA transcription and replication after irradiation, types of cell death after irradiation – apoptosis, necrosis, mitotic death, autophagy
  • DNA damage repair: BER, NER, NHEJ, homologous recombination, alternative repair pathways
  • Histone code, higher-order chromatin architecture and epimutations
  • Cytoplasmic effects and bystander effects
  • Applications of ionizing radiation in medicine – Radiotherapy and theranostics
  • Principle of radiotherapy – response of normal and cancer cell types to irradiation, external radiotherapy, fractionated irradiation, modern approaches in radiotherapy, brachytherapy, boron-capture therapy
  • Hadron therapy – protons and accelerated heavy ions with high LET (also in the context of planned space missions), physical features favoring high-LET ions for radiotherapy, “economic toxicity” of hadron therapy.
  • Tumor radioresistance – hypoxia, oxygen enhancement ratio (OER), genetic factors (e.g., p53 mutations), radioresistant tumor clones’ selection by (radio)therapy
  • Current and future possibilities of normal cell radioprotection and tumor cell radiosensitization – physical (metal nanoparticles), chemical (amifostin), and biological (inhibitors of DNA repair, immuno-modulators, etc.) modulators of cell radiation survival

Lecture 13 + 14: Natural and man-made sources of ionizing radiation, radiation protection, biophysical and molecular biology methods in radiation research; news in radiobiophysical/radiobiological research

  • Natural sources of ionizing radiation
  • radon
  • terrestrial sources
  • cosmic rays
  • Man-made sources of ionizing radiation
  • Ionizing radiation in radio-diagnostics and radiotherapy
  • Fallout and contamination from atomic bomb testing
  • Professional exposures
  • Average radiation absorbed doses in everyday life and specific activities; health risks

 

  • Basics of radiation protection
  • external exposure
  • internal contamination
  • biogenic radionuclides
  • protection strategies against different types of ionizing radiation
  • Methods in radiation biophysics research
  • cell cultures, tumor cell primocultures and experimental animals
  • clonogenic survival
  • flow cytometry and tests of cell viability
  • microscopic and super-resolution microscopic techniques to analyze DNA damage and repair in single cells, under specific cell states, and at individual DNA damage sites
  • comet assay
  • pulse-field gel electrophoresis (PFGE) methods of genomics and proteomics, etc.



 

Wahlpflichtbereich 4 LP. Der Leistungsnachweis wird durch eine Klausur erbracht.

Termin der Klausur: wird noch bekannt gegeben (Klausurdauer max. 60 min)

Termin der Nachklausur: wird noch bekannt gegeben



 

Inhalt:

Ionisierende Strahlung (UV-Strahlung, Röntgen Strahlung, Radioaktive Zerfälle, Elektronen-, Protonen- Ionen-Strahlung etc.) stellt nicht nur eine unabänderbare Komponente unserer Umwelt und damit der Entwicklung zellulären Lebens dar sondern trägt bis heute entscheidend zur modernen medizinische Diagnostik und Therapie bei. Während die Physik der molekularen Schadensinduktion den Regeln der Quanten- und festkörperphysik unterworfen ist, greift die zelluläre Antwort auf ein komplexes System von Regel- und Steuerkreisen zurück, die sich im Laufe der Evolution als vorteilhaft für das funktionelle Überleben zellulärer Systeme erwiesen haben. Um einerseits die Strahlenwirkung im Hinblick auf einen personalisierten Einsatz in der Medizin besser nutzen und andererseits Grenzwerte im Strahlenschutz wissenschaftlich begründet festlegen zu können, ist ein vertieftes transdisziplinäres Verständnis der Wechselwirkungsmechanismen der Schadensinduktion und -reparatur nach Strahlenexposition Gegenstand moderner Forschung.

Die Vorlesung soll aufbauend auf den allgemeinen Grundlagen der Biophysik in die speziellen Grundlagen der Strahlenbiophysik und der aktuellen Forschung hierzu einführen. Es werden folgende Themen betrachtet:

- Radioaktiver Zerfall und Erzeugung ionisierender Strahlung

- Wechselwirkung und Absorption ionisierender Strahlung und hochenergetischer Teilchen mit Materie

- Extremophile Lebensformen

- Charakteristische Größen der Strahlenbiophysik und Dosimetrie

- Prinzipien und Messgrößen im Strahlenschutz

- natürliche und technische Strahlenexposition des Menschen

- zelluläre Wechselwirkungen und DNA Schädigung durch ionisierende Strahlung

- Strahlenrespons und DNA Reparatur

- Biologische Dosimetrie und Co-Faktoren

- "gute" und "böse" Strahlung, Dilemma des Strahlenschutzes

- UV-Strahlung und Lebensentwicklung

- Einblicke in moderne Forschung der Strahlenbiophysik



 

 

 


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