Tuesday, December 09, 2014

Nanomimics of Host Cell Membranes Block Invasion and Expose Invasive Malaria Parasites

Nanomimics of Host Cell Membranes Block Invasion and Expose Invasive Malaria Parasites.

For many infectious diseases no vaccine currently exists. In addition, resistance against currently used drugs is spreading rapidly. To fight these diseases, innovative strategies using new mechanisms of action are needed. The malaria parasite Plasmodium falciparum that is transmitted by the Anopheles mosquito is such an example. Malaria is still responsible for more than 600,000 deaths annually, especially affecting children in Africa (WHO, 2012).

Artificial bubbles with receptors

Malaria parasites normally invade human red blood cells in which they hide and reproduce. They then make the host cell burst and infect new cells. Using nanomimics, this cycle can now be effectively disrupted: The egressing parasites now bind to the nanomimics instead of the red blood cells.

blood cells

After maturation, malaria parasites (yellow) are leaving an infected red blood cell and are efficiently blocked by nanomimics (blue). (Fig: Modified with permission from ACS).

Researchers of groups led by Prof. Wolfgang Meier, Prof. Cornelia Palivan (both at the University of Basel) and Prof. Hans-Peter Beck (Swiss TPH) have successfully designed and tested host cell nanomimics. For this, they developed a simple procedure to produce polymer vesicles – small artificial bubbles – with host cell receptors on the surface. The preparation of such polymer vesicles with water-soluble host receptors was done by using a mixture of two different block copolymers. In aqueous solution, the nanomimics spontaneously form by self-assembly.

Blocking parasites efficiently

Usually, the malaria parasites destroy their host cells after 48 hours and then infect new red blood cells. At this stage, they have to bind specific host cell receptors. Nanomimics are now able to bind the egressing parasites, thus blocking the invasion of new cells. The parasites are no longer able to invade host cells, however, they are fully accessible to the immune system.

The researchers examined the interaction of nanomimics with malaria parasites in detail by using fluorescence and electron microscopy. A large number of nanomimics were able to bind to the parasites and the reduction of infection through the nanomimics was 100-fold higher when compared to a soluble form of the host cell receptors. In other words: In order to block all parasites, a 100 times higher concentration of soluble host cell receptors is needed, than when the receptors are presented on the surface of nanomimics.

“Our results could lead to new alternative treatment and vaccines strategies in the future”, says Adrian Najer first-author of the study. Since many other pathogens use the same host cell receptor for invasion, the nanomimics might also be used against other infectious diseases. The research project was funded by the Swiss National Science Foundation and the NCCR “Molecular Systems Engineering”.

Original source: Adrian Najer, Dalin Wu, Andrej Bieri, Fran├žoise Brand, Cornelia G. Palivan, Hans-Peter Beck, and Wolfgang Meier
Nanomimics of Host Cell Membranes Block Invasion and Expose Invasive Malaria Parasites. ACS Nano, Publication Date (Web): 29 November 2014 | DOI: 10.1021/nn5054206

Further information: Prof. Wolfgang Meier, University of Basel, Department of Chemistry, phone: +41 61 267 38 02, email: wolfgang.meier@unibas.ch

2 comments:

Alien Contact said...

(I have a materials science solution to pandemics):
I’ve been given a framework and figured out many details, to terminate pandemics and goos that would metastasize the biosphere in the future. I’m not presently able to critique if it is a trap. This is possible in 50 years (in time) but realistic in a century; too late if the present synthetic biology trajectory and to a lesser extent insect/pollen/micro/nano drone materials science trajectory is maintained.
The idea is to section the atmosphere/surface up to 5km high, as well as the lithosphere down to 3km, into a series of cubes. There will be 5km high towers enclosing (9km^3) a one metre diameter helium interior column, regularly spaced along Earth’s surface every 1.8km. The connected towers covering Earth will each enclose 200m x 200m x 200m volumes (resembling giant skyscraper suites) encased by a one micron diamond layer (ignore the accompanying sensors for now to prevent AI R+D). Goo needs 100km/hr to break through a diamond plate. A new “Eagle Eye” explosive is placed every 27-64 cubes and must reach any goo/pandemic in one minute through holes (air supply) in the diamond plates with filter/mesh keeping out drone parts. Backup is a nuke every 30 x 30 buildings or 100000km^2. 100 sane Generals in each jurisdiction are each able to individually arm the nuke within one minute of goo detection/spreading. The nuke takes out a building. Rail guns accelerate the nuke using PR immediately upon detection to Mach 25 through subway tunnels spanning Earth. 5000 nukes. A possibly impossible 100 scram jet nuke payload system is a redundancy (as are space colonies) travelling Mach 60 or Mach 100, and able to immediately course correct or launch super-rapidly-accelerating nuke “lifeboats” can be armed by one of 1000 global Leaders within one minute or arm 7 within 80 seconds (lesser success odds). Alternative is 166666 nearly stationary nukes. Too fast railguns is risky. I assume many nukes must deactivate or become less trigger happy once a few dozen or less have been detonated…each cube has a sensor for noticing pandemics or goo or spreading goo as well as manufacturing (implements) of such.
Subterranean requires copper enclosed cubes 30m x 30m x 30m until 200C at 3km depth. Copper one mm think (or aluminum 1 cm thick) is buried with a sensor layer (1mm plastic). A vibration sensor in the plastic is enough to detect most goos, which take 2-3 hours to get through copper. Pre-made tunnels through the lithosphere deliver one nuke within 2-3 hours or 10000 nukes (all) in a day. Longer is Revelations and more than one nuke (one cube) simultaneously detonated; you aren’t really sure if you destroyed target. Neutrinos (not flavour changes) can be used to detect density changes in Earth’s lithosphere.
Oceans are cubed 2km x 2km x 2km with 1 or 2mm mesh having sensors that prevent any larger object from penetrating as well as facilitating a random check of microscopic life every few metres. Acoustic shockwaves mines will be invented that function like nukes (blastwave 2km in radius). It ruptures all metastasizing substrates that are soft enough to be used quickly enough to escape destruction using conventional naval arms of the future. It will getaway and ruin the oceans if it controls more than 300-400km^2. Tiny torpedoes will destroy the replicators after a shockwave is used in a given volume.
I’ve classified the 2 dozen technologies and had help with 28%, and got 10% wrong.

Alien Contact said...

...
Easy:
-The rocket/jet that rapidly carries a nuke payload above 5km up to I assume LEO.
-Response for nuke accidents/terrorist attacks.
-PR used so nukes immediately head towards detected pandemics/goos.
-Tower/diamond-plate support structure and design.
-“Eagle Eye” explosives.
-Holes with filters/mesh in diamond plates along with transport system for future explosives rapid delivery.
-1000 members of the world’s Executive Branch, each able to detonate one or 7 nukes of scram jets (assuming scram jet redirect possible and assuming glitches okay but not a nuke winter level glitch).
-(Subterranean) Vibration sensor in copper.
-(Ocean) 1 or 2mm mesh with sensors.
-(Ocean) Little torpedoes.
Medium:
-Plates of diamond.
-100 Generals each able to detonate a nuke in 100000km^2 jurisdiction if sane, within a minute.
-(Subterranean) Tunnels for 5000 nukes to reach towers quickly.
-(Subterranean) Rail gunned nuke hitting Mach 25 for above.
-(Subterranean) 1mm thick copper (or 1cm Aluminum) as well as any sensor substrate such as 1mm plastic, every 30m underground (27000m^3 cubes) down to 3km and 200C replication maximum temperature.
-(Ocean) Acoustic shockwave mines that function like nukes.
Hard:
-Massive diamond manufacturing facilities (about 27km^3 in giant thin plates).
-Detection above 5km of goos/pandemic (RADAR but ice and dust complicates).
-Sensor(s) in each diamond cube for detecting pandemics/goos and manufacturing of such.
-5km high towers with helium filled one metre diameter interior, gridding Earth.
-(Subterranean) Using neutrinos to detect underground density changes (goo).
-(Subterranean) Lots of pre-made underground tunnels to deliver nukes(s) to underground copper cube in time.
-(Subterranean) One day’s delay, 10000 nukes to possibly stop underground goo.
Maybe Impossible:
-100 Scram Jets with nuke payloads continually in flight able to be redirected or launch a superfast payload to a different trajectory and reach target within one minute.
-Same but 7 nuke configuration with 80 second ETA and less certainty of efficacy.

Post a Comment