Crossing the Frontiers

Published in JFWTC inhouse journal  Vol.4 Issue 1-2 (2008)

That geographical boundaries are never  barriers in the pursuit of science is once again  reinforced  in the  12^th June issue of Nature.  This issue  carries a  very important paper  by    29 scientists  from 4 nations on  how Gama Secretase Modulators ( GSM)  act  (1).    Gama secretase  is the   key  enzyme  which chops up the  Amyloid Precursor Protein (APP)  into  fragments.   Of these fragments,   the 42 residue long beta amyloid peptides  cling together  to form the debris patches responsible for  Alzheimers’s disease.  The shorter fragments are (as of now) considered harmless because they don’t lump together .

Modulators  are small chemical molecules which  as the name implies, influence the activity of an enzyme. For example  ibuprofen  modulates gama secretase to preferentially produce only the  short fragments.   The global team had a very clear objective in mind: to find out the mode and site of action of  ibuprofen like  modulators.   This then could pave for the design/identification  of more powerful modulators to effectively counter the progress of Alzheimer’s disease.   Usually, molecules such as modulators, inhibtors or enhancers,  bind to the  enzyme itself and alter its  ability to bind to substrate.   However  the team was surprised to find that the  GSMs actually  sat at strategic positions on the  substrate APP and prevented  the  enzyme from making larger cuts!   So now there is a rush to screen and identify  the best of the lot and pharmaceutical firms are already smelling  billions of  dollars in profit.

The same issue of Nature describes the possibility of pH imaging of tissues in vivo (2).   GE Healthcare is an industry partner in this work done in collaboration with University of Cambridge.  The assumption here is that tissue pH is  indicative of  the tissue health. So can we measure or map it ?  The team injected  hyperpolarized ¹³C enriched bicarbonate solution into mouse having subcutaneous lymphoma. They then   measured the signals of  H ¹³CO₃ ^-  and  ¹³CO₂  using  MR .  pH could then be calculated from the age old Henderson-Hasselbalch equation.   This paper  has  two significant take aways   yes  the tumor pH is lower than the surrounding tissue pH and  yes, it is possible to measure tissue pH in a quick,  noninvasive way.

The 8^th World Congress on Biomaterials held at Amsterdam from 29^th May till 1^st June had an apt subtitle: Crossing of Frontiers.  The Congress, held once in 4 years facilitates  interactive sessions not only on Biomaterials  but also on all relevant adjoining scientific disciplines.  It was indeed a crossing of frontiers of materials, medicine and biology on one hand and academy and industry on the other.  The wide range of  perspectives that these  groups brought to the discussion table  facilitated innovative collaborations.

The Congress was just intense. I have never poured over a conference abstract book with so much thoroughness.  With 9 parallel oral presentation sessions from  8.45 AM till 5.30PM and  15 clusters displaying close to a total of  1600 posters,  it was necessary to do some homework.     Sitting  late into the night  I marked  the specific oral and poster presentations  I must not miss at any cost.   

“Layer by layer nanoassembled biomaterials”  was one such  theme.     Often referred to as LBL , this technique  is an area of intense research today because of the  innumerable possibilities it offers,  in terms of  structure and function of the ultimate product.   Akashi’s  group from Osaka University  presented the their elegant work on the fabrication of  cellular multilayers on  gelatin and fibronectin  films. 

On Nanopatterning    IBM research group at Zurich  in collaboration with  Georgia Tech,  demonstrated  how the simple technique of microcontact printing   could be used to get not only  protein arrays but  entire  protein libraries on a  substrate surface.    MAPS (Microstamping onto an Activated Polymer Surface)   a new acronym  that caught on fast,   refers to  the process of  patterning  biological ligands and proteins onto the surface of polymers.

 Three dimensional scaffolds for tissue engineering  was another actively deliberated  theme.  Spanned across  several sessions  participants presented new data on  synthetic and natural polymers, composites, hybrid hydrogels,  electrospun systems,  etc. with spherical and cylindrical geometries getting special attention.  The symposium on “ what intrinsic information content is required of the scaffold  in the tissue engineered constructs” was an attempt to set  some guidelines on the selection of the scaffold chemistry and geometry depending on what needs to grow on it.

Hydrogels  continue to be  the most preferred  biomaterial  for many applications.  I was pleasantly surprised and indeed proud  when several of our papers  published a decade ago were cited  in connection with synthesis and characterization of Polyethyleneglycol  hydrogels.  

Tail piece :

The  Biomaterials Congress  opened with the enactment of Rembrandt’s “Night Watch”.  The characters marched to the stage to the accompaniment of the drum beat and took up their positions as if ordained by Rembrandt.  For a moment we were transported to the Rembrandt era  till we saw one of them easing out of the cluster and go to  the mike to address the audience.  There is an interesting addendum to the “Night Watch”.  History states that  all those in the  painting actually paid Rembrandt  to be there, except perhaps  the drummer.

1.Substrate targeting g Secretase Modulators:

   Kulkar etal  Nature 453,  925- 929  ( 12 June 2008)

2. Magnetic resonance imaging of pH using hyperpolarized ¹³C labeled bicarbonate

   Gallagher et al  Nature 453, 940-943 (12 June 2008)

3. World Biomaterials Congress   http://www.wbc2008.com/