Brain Science Technology

In the process of conducting its basic and applied research programs, BRNI scientists have developed technologies that can accelerate and more accurately quantify the results of a variety of diverse experimental protocols.  These technologies could have general application not only for BRNI research but also for research conducted in many laboratories with diverse experimental objectives.  Examples of such technologies are listed below.

Image Analysis and Quantification

For many biochemical analyses, the density of bands on chromatographic images must be quantified to assess specific measures such as protein phosphorylation.  Dr. Tom Nelson has developed an algorithm that identifies the maximum density of a given band and then quantitatively compares that density against a standard background.  This method has greatly improved the analyses of a number of biochemical measurements including those used for our Alzheimer’s diagnostic peripheral biomarker.

Protein-Protein Interaction 

Another of these technologies screens for completely unknown proteins and their interactions in memory and other cognitive functions.  Using a chromatographic separation procedure known as two-dimensional gels, protein-protein interaction profiles have been found to consistently characterize physiologic and pathophysiologic brain functions.  Such profiles can then be used in conjunction with mass spectrometry to reveal previously unknown proteins that are participating in the protein-protein interactions unique to a particular function or a particular pathologic transformation of that function.  With this technology, BRNI researchers have discovered important new classes of proteins responsible for synaptic remodeling during memory storage. This same type of protein-protein profiling should be helpful for characterizing other aspects of memory storage, for example, extinction, as well as for identifying unique pathologic changes in brain disease.  Similarly, protein-protein profiling will help identify drug targets as well as potential causes of drug toxicity.

Blood-Brain Barrier (BBB) Transport

The blood-brain-barrier is a natural protection that prevents the entry of infectious organisms into the brain.  This same barrier, however, often prevents brain access to a number of potentially beneficial agents that might treat infectious disease, tumorigenesis and neurodegeneration.  To increase brain accessibility to potentially beneficial drugs as well as imaging agents, BRNI scientists have developed a method for crossing the blood-brain-barrier.  This method uses natural particles that are used by the body to transport proteins.  These LDL (low density liproprotein) particles can be converted into a carrier that holds agents of interest within the particle.  The particle is then coated on its external surface with natural proteins such as a proteins called ApoE that are recognized by receptors located on the BBB.  The LDL particle then “docks”: on the ApoE receptor and enters into a transport process called “transcytosis”.  The net effect of this transyctosis is to transport drugs across the blood-brain-barrier.

Institute scientists have already demonstrated that the LDL-transcytosis method greatly enhances brain access of drugs such as tetracycline that ordinarily not efficiently reach brain tissues.  BRNI's recently patented BB transporter technique could bring a variety of drugs into the brain to treat brain tumors, Alzheimer's disease, depression and brain infections such as meningitis and encephalitis.