Matt Gethers/20.380 HIV Project/Meeting Notes/3.4.08 (Final Cut on Design Ideas): Difference between revisions
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*Exploding RBCs? - '''David''' | *Exploding RBCs? - '''David''' | ||
*Any natural conditions where RBCs die or explode? - '''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''' | *Take out hemoglobin? Anything else to knock out? - '''Yi''' | ||
*Pathologies of RBCs - esp. sickle cell anemia, thalassemia - '''Yi''' | *Pathologies of RBCs - esp. sickle cell anemia, thalassemia - '''Yi''' |
Latest revision as of 03:52, 18 March 2009
3.4.08 (Final Cut on Design Ideas)
To Do
Make list of issues/questions to consider in implementing the engineered T-Cell idea.
Make list of issues/questions to consider in implementing the engineered RBC 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
Make list of issues/questions to consider in implementing the superinfection idea.
Questions
- Does superinfection apply across strains?
- Fidelity of superinfection? How often does it fail?
- Matt
- Divide work for presentation next week (3/12/09)
- Modify calendar to reflect changes in schedule.
Minutes
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?)
- Need to start with hematapoeic stem cell