User:Johnsy

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#My best place to relax:  a remote island in the Philippines
#My best place to relax:  a remote island in the Philippines
#One thing I can't live without:  internet...:)
#One thing I can't live without:  internet...:)
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==20.310 Term Paper==
 
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===TItle===
 
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Analysis of Human Immunodeficiency Virus Type I gp120 Receptor Interactions and its Implications on Future HIV Drug Therapy.  (A single paper critique)
 
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===Abstract===
 
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In ''Single-Molecule Analysis of Human Immunodeficiency Virus Type 1 gp120-Receptor Interactions in Living Cells'', the authors give a quantitative description of the binding forces and dissociation constants of the gp120/CD4/CCR5 receptor complex using a molecular force probe.  Experimental data is fitted to the Bell model relating the rupture force required to break a bond between two molecules to the applied loading rate.  The breakthrough proposed in this paper is providing a quantitative analysis of the forces involved in viral-host cell interactions which may lead to a better understanding of the mechanisms of viral infection.  Once we successfully elucidate the molecular mechanism of viral entry, we can then propose innovate drug treatments capitalizing on HIV-1 entry inhibition.
 
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The experimental method used by Chang, et al., is similar to the use of atomic force microscopy experiments we learnt in class to determine forces.  They use a cantilever with the gp120 receptors attached and use it to probe the cell surface membrane containing only the CD4 host receptors, only the CCR5 chemokine receptors, or a combination of both receptors.
 
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Although experimentally it was shown that the force required to break the gp120/CD4/CCR5 bond was similar to that required to break the bond between gp120 and CD4, the bond between formed between all three coreceptors lasted significantly longer than the gp120-CD4 bond. 
 
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Studies have been shown that persons with a delta32 mutation coding for the CCR5 have a much lower HIV infection rate than individuals that are wild type.  Thus, understanding the mechanics behind the CCR5 interaction with the gp120 receptor protein could help in elucidating why such individuals with mutations have a much lower prevalence of HIV.  This could be significant in leading to therapies aimed at modulating the receptor binding, potentially affecting the lives of millions of AIDS sufferers.
 
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===Paper Outline===
 
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*Introduction
 
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**The gp120, CD4, CCR5 interactions involved in viral entry
 
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**Current qualitative understanding of mechanism
 
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**Aims of the paper to eludicate a quantitative mechanism for HIV-1 entry into cells
 
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**Delta32 Polymorphisms leads to lack of CCR5 and HIV resistance
 
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*Methods
 
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**Use of single-molecule force spectroscopy (adaptation of atomic force microscopy)
 
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***Combations of gp120, CD4, and CCR5 used in assay
 
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**Why did they use the apparatus they did?
 
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**What could be improved on in their setup?
 
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**What experimental factors could have contributed to error?
 
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**Ensuring single molecule interactions
 
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***Force applied lowered to reduce surface area of contact
 
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***Cantilever and cell interaction less than 1 ms
 
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***Density of gp120 made low
 
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*Results
 
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**gp120 binding to CD4 or CD4/CCR5 force is similar
 
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**Use of Bell model for analysis
 
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**Stronger binding interactions between gp120 and CCR5 than gp120 and CD4
 
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**Dissociation time longer for gp120/CD4/CCR5 than gp120/CD4
 
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**Did their experimental data confirm the hypotheses?
 
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**Are there any assumptions with the parameters and equations?
 
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*Future Prospects
 
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**HIV therapy
 
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**Similar appraoch can be used to elucidate other viral entry mechanisms
 
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===Prelimiarly Bibliography===
 
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<biblio>
 
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#Chang1 pmid=16282475
 
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#Doms00 pmid=11069884
 
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#Doranz99 pmid=10559353
 
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#Hanley03 pmid=12522146
 
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#Hill97 pmid=9261346
 
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#Kwong98 pmid=9641677
 
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#Pierson04 pmid=15248253
 
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#Pohlmann02 pmid=12462149
 
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#Sun06 pmid=16284274
 
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#Wu96 pmid=8906795
 
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#Urnov00 pmid=15806097
 
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</biblio>
 

Revision as of 23:21, 23 February 2007

John Sy

Contact Information:

E-mail: john.sy (at) imperial.ac.uk, syjohn (at) gmail.com, syjohn (at) mit.edu

MIT Spring 2007 (Tentative)

  • 7.02 Biology Lab or 20.109 Biological Engineering Lab
  • 7.06 Cell Biology
  • 20.330 Fields, Forces, and Flows in Biological Systems
  • 21W.703 Expository Writing

MIT Fall 2006

Imperial iGEM

Education

Interests

  • Sport – Swimming and Badminton
  • Travel – Travel over Europe, Asia, Africa, and North America
  • Arts – frequent concerts, plays, and musicals as well as enjoy visiting art galleries and reading classics

More Random Stuff About Me

  1. Favourite Colours: Orange & Blue
  2. Ethnic Origin: Chinese from the Philippines
  3. Place I would like to retire: somewhere in the USA
  4. Quote I like: "God grant me the serenity to accept the things I cannot change, to change the things I can, and the wisdom to know the difference"
  5. Religious Affiliation: None
  6. What I wanted to be when I grew up: pilot, businessman, lawyer, among other things
  7. What I want to do now: medicine
  8. Places I haven't been that I want to go: Australia & New Zealand
  9. My best place to relax: a remote island in the Philippines
  10. One thing I can't live without: internet...:)
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