Slide sem ttulo

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Application of Synchrotron Radiation in
Nanobiotechnology and Biotechnology Dr. N.
Moazami October 11, 2004
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Lessons from Nature

• Billion of years ago, Molecule began organizing
  themselves into the complex structures that could
  support life.
• Nano-biotechnology is a new word, but it is not
  an entirely new field. Nature has many object and
  processes that function on a micro to nano scale.

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Biological and life Sciences

• Most of the biological functions (from
  respiration to digestion) involve very large
  molecule, the biological macromolecules
  (proteins, enzymes, viruses, ...).
• The function of a biological macromolecule is
  directly linked to its structure, i.e., its
  spatial arrangement. The knowledge of this
  structure is a major goal for scientists.
• Structure function studies, particularly the
  quantitative identification of the atomic
  assembly of large biomolecules and the
  determination of the microstructure of biological
  tissue (muscle, ligament, tendon) in dynamic
  situations.

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NanoBiotechnology Definition

• Is the use of biological systems as templates in
  the development of novel Nano-Scaled products.
• Scientists have developed a way to use DNA for
  minuscule wires that can be used in
  nano-electronics.
• Ability to have insulated wires sized at 25nm and
  20 microns in length.

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Leading Segments in Nano-Biotechnology

• - Drug Delivery
• Bioavailability
• Sustained Release
• Targeted Delivery
• Targeted Release
• -Imaging Agents
• Magnetic Resonance Imaging (MRI)
• Near Infrared Fluorescence Imaging
  (NIRF) combined with MRI
• Drug Discovery
• Rapid Ex-Vivo Diagnostics
• -Biosensors
• In Vitro Application Basic Research
• Diagnostic Application Implantable
  Diagnostic Devices
• Internal Diagnostics
• Intracellular Diagnostics

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Nanotubes

• Conductive and
• high-strength composites
• Energy storage and
• energy conversion devices
• Sensors
• Medical drug delivery and DNA research
• Nanometer-sized semiconductor devices, probes,
  and interconnects

Nanotubes are built by arrangingseveral atoms
in a closed pattern to form an unbelievably
small tube
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Nanotubes Applications in Bio-nanotechnology

• Biosensors
• Drug Discovery
• Drug Delivery
• Imaging Agents

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The Machine of Life

• The Genomes to Life facilities roadmap
  proposes a facility for characterization and
  imaging molecular machines.
• This facility is to focus on structural and
  biophysical analysis of macromolecular complexes
• (the machines of life).
• The atomic or nearatomic resolution of the
  RNA polymeraseII complex of the Ribosome and its
  subunits, of the ATPase and of the Proteasome
  all show the remarkable power of macromolecular
  crystallography in providing a structural
  foundation for understanding the biophysics of
  very large molecular machines.

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The Machine of Life
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Life Function
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Application of Synchrotron Radiation

• The SR techniques used for structural biology
• can be subdivided into four principal areas
• Crystallography, Spectroscopy, Scattering from
  nonocrystalline materials and imaging.
• The first major step in the biotechnology
  revolution was unraveling the structure of DNA.
• During the past ten years the number of protein
  structures elucidated by Xray crystallography
  has risen more than ten fold.
• At last count there were more than 17,000 protein
  structures available in the protein Data Bank.

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Synchrotron Radiation Specificity

• The unique properties of the synchrotron
  radiation are its continuous spectrum, high
  spectral flux and brightness, tenability and the
  relatively high coherency which makes this type
  of radiation a powerful tool for experimentalists
  to describe the nature of the microworld and to
  develop new approaches in industrial applications
  at the molecular and submolecular level.
• Synchrotron Xradiation is a critical resource
  for structural biology. Synchrotronbased Xray
  photon techniques make unique contributions to
  understanding biological structure and function.

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Pharmaceuticals

• Perhaps the most widely known industrial
  application of synchrotronbased research, and
  perhaps the most economically
  significant in the near term, is in the
  exploration of protein structures.
• Pharmaceutical companies appreciate the rapid
  data collection on very small crystals at higher
  resolution than with conventional Xray sources
  for the research and development of innovative
  medicines.
• Traditional methods of drug development, based on
  the identification and isolation of active
  ingredients, selection involve a high degree of
  risk both in the drug development cycle and in
  the control of side effects.

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Applications of InterestHealth monitoring,
micro-dose drug release
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Medicine and health care

• The everincreasing contributions of
  hightechnology science to medical practice will
  continue.
• Biocompatible materials, surface modifications
  and coatings are required for the production
  of artificial tissues, bone, implants, grafts,
  Joints and medical devices.
• Rapid diagnostic kits, including those sold over
  the counter for selfdiagnosis, will become
  commonplace, Biologically active electrochemical
  sensors will be developed to provide therapy,
  preventative action and biofeedback to controlled
  drug delivery.

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Tissue Engineering

• Several Technologies come together in tissue
  engineering.
• Large-Scale culturing of human or animal cells
  -including skin, muscle, cartilage, bone, marrow,
  endothelial and stem cells may provide
  substitutes to replace damaged components in
  humans.
• Naturally derived or synthetic materials may be
  fashioned into Scaffolds that when implanted in
  the body.
• Pancreatic beta cells required to produce Insulin
  may be encapsulated in engineered bimolecular
  cages that allow them to function normally in a
  foreign host without triggering immune responses.
• Biocompatible polymers may be developed to cover
  implants and shield them from adhesion of
  circulating proteins that initiate rejection
  responses.

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Tissue Engineering Process
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Diatoms Frustules Structure
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Diatom Cell Wall
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Coralline Hydroxyapatite Bone Graft

• The Idea of using coral as a replacement for a
  bone graft came when looking at the structure of
  the limestone skeleton of these marine
  invertebrates.
• Coral skeleton is composed of more than 90
  aragonite (CaCO3) is very close chemically to
  mineral bone.
• During the last 16 years, natural coral skeleton
  has been successfully used as a bone substitute
  in most surgical fields.
• Coral implant presenting excellent
  biocompatibility and osteoconductive properties.

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Corals Skeleton Structure
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Regeneration of Bone by Tissue Engineering
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Medical Imaging and Radiation Therapy

• - Application of synchrotron X ray beams for
  medical purpose has become an important part of
  the synchrotron radiation use and opens an
  opportunity for better medical center.
• - The highlights for medical therapy and
  diagnosis by use of synchrotron radiation light
  source include
• Angiography
• Bronchography
• Mammography
• Computed Tomography
• Photon Activation Therapy

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• Structural Biology
• Structural biology research is producing results
  of high biological impact that have a direct
  bearing on human health issues. Structure based
  drug design, which seemed merely a trendy phrase
  a few years ago, has become a reality.
• Structural biology is also becoming increasingly
  important in biotechnology, as for example, in
  the design (or redesign) of enzymes to degrade
  pollutants or to act as thermostable industrial
  catalysts or in the design of insecticides with
  increased efficacy.
• These applications can have huge environmental
  and economic impacts.

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• Macromolecular Crystallography
• A Macromolecular crystallography beam line is
  dedicated to the determination of the
  3dimensional structure of large biological
  molecules using Xray diffraction.
• The scientific and application research program
  on the macromolecular crystallography using
  synchrotron radiation
• include a broadband problems related to life
  sciences
• -High Capacity Crystallography
• -Enzyme Mechanism
• -Supramolecular structure
• -Molecular Recognition
• -Nuclear Acids
• -Structural Genomic
• -Protein Structure
• -Drug Design

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Macromolecular Crystallography
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Microbiology and Protein Crystallography

• All cells of higher animals and plants contain a
  small organelle or compartment whose primary role
  is to generate the energy required to drive the
  numerous chemical reactions that keep the cell
  alive.
• This compartment is called the mitochondrion.
• Electron microscope images taken 30 years ago
  showed that ATP-synthase resembled a lollipop
  in shape ,with a roughly spherical head about 100
  m across.
• The very intense X-ray beam of Synchrotron system
  determined that the structure reveals that the
  spherical head made up of six individual protein
  chains packed together like the segments of an
  orange.
• Relating the method of coupling the proton flow
  to the generation of ATP will answer one of the
  central questions in understanding how the
  mitochondrion works as the power house of the
  cell.

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Mitochondrion
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Microbial ATPase
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Conclusion Remarks The general demand for
structural information in all molecular fields of
biology continues to grow very rapidly, and is
paralleled by a growth in the demand for
synchrotron time. Three factors contribute to the
substantially increased demand a Technological
improvements in synchrotron facilities,
Xray detectors. b As the complexity
of the biological project increases, there is a
greater demand for synchrotron time to tackle
more difficult problems. c As anticipated a
significant new demand has indeed come from a
latent community of users who are not
specialists in crystallography but who have
biologically significant structure determinations
to carry out.
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• There is a strong demand for regional facilities
  that can provide service to the regional
  scientific community.
• It was deemed of extreme importance that
  research groups be within driving or short flying
  with distance of synchrotron facilities to
  exploit their resources fully.
• The ability to a local facility with samples in
  hand was rated as extremely important by a
  majority of users.
• Graduate students and postdoctoral fellows are
  the majority of scientific workers who actually
  go to the synchrotron, and it is essential that
  proximity to synchrotron facilities allow them to
  travel in
• large numbers for training.

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• Thanks
• for
• Your Attention