Matt Gethers/20.380 HIV Project/Meeting Notes/3.4.08 (Final Cut on Design Ideas)

=3.4.08 (Final Cut on Design Ideas)=

To Do
Make list of issues/questions to consider in implementing the engineered T-Cell idea.

Questions

 * What do we need to put into the person? What stage of progenitor cells? - (done!)
 * Immunity issues with progenitor cells? - Rob
 * How are RBCs removed/recycled from body? - Courtney
 * Can HIV infect progenitor cells? - Matt
 * How to couple CD4 expression, etc with RBC differentiation? - Rob
 * Malaria - Courtney
 * What's necessary and sufficient for HIV infection? - Matt
 * What to do with HIV once in cell? Do we need it to do anything? - Rob
 * How to prevent HIV from leaving RBC? - Jessie
 * Death switch? - Jessie
 * Exploding RBCs? - David
 * Any natural conditions where RBCs die or explode? - David
 * A normal erythrocyte has a volume of about 90 fL=9.0 X 10^-17 L (a third of which is hemoglobin only freed up if we knock it out)
 * HIV is roughly a sphere of diameter 120nm --> volume of 9.05 X 10^-22 L
 * A normal RBC can theoretically hold a maximum of ~100,000 HIV virions if it has nothing else inside, including water
 * Damaged/misshapen RBCs are naturally destroyed in the spleen (i.e. anything but biconcave cells)
 * There is an entire class of disorders classified as "Hemolytic anemia" where RBCs are broken down prematurely/too much (http://en.wikipedia.org/wiki/Haemolytic_anemia)
 * Some are congenital
 * misshapen membrane
 * metabolic defects
 * sickle-cell anemia
 * thalassaemia
 * Some are acquired
 * autoimmune disorders
 * some drugs (ribavirin)
 * toxins
 * malaria and some other infections
 * Questions:
 * How many copies of HIV do we expect each RBC to hold? (question for modeling)
 * Can't find any papers on what happens when HIV virions aggregate in a small volume (could anything bad/unexpected happen? cross-linking?)
 * If we knock out hemoglobin, do we need to worry about too little osmotic pressure inside? Is Hb just replaced by ions from blood?


 * Take out hemoglobin? Anything else to knock out? - Yi
 * Pathologies of RBCs - esp. sickle cell anemia, thalassemia - Yi
 * Ideal concentration of RBC progenitors? - Steph
 * How to get into bone marrow? Easy injection method? - Steph
 * Role of progenitors? - Steph

Questions
- Matt
 * Does superinfection apply across strains?
 * Fidelity of superinfection? How often does it fail?


 * 1) Divide work for presentation next week (3/12/09)
 * 2) Modify calendar to reflect changes in schedule.

Minutes
Seven Ideas

=Follow Up=

Erythropoiesis

 * Cell Lineage Map
 * Need to start with hematapoeic stem cell
 * knock out other lineages? (maybe we could leave them? would it be a problem?)