161phagosome proteome. Phagosomes are required by macrophages to participate in
tissue remodeling, clear dead cells, and restrict the spread of intracellular patho-
gens. The systematic characterization of phagosome proteins provided new insights
into phagosome functions and the protein or groups of proteins involved in and
regulating these functions.
An example of the utilization of the knowledge of pathomechanism of disease is
the selection of key families of proteins such as G-protein coupled receptors (GPCR)
and ion channel transporters that are well-established targets for intervention in
disease. Maps of distribution of these proteins are available and are evaluated in the
context of genomics, pharmacology and clinical information. This has led to identi-
fi cation of novel mechanisms for therapeutic intervention.
Single Cell Proteomics for Personalized Medicine
Owing to the complexity of the intracellular metabolic pathways, an understanding
of the intracellular pathways has been lagging behind the advances in gene expres-
sion. Recently, multicolor FACS (fl uorescence activated cell sorting) techniques
combined with phosophospecifi c antibodies have been developed, enabling the
determination of relative phosphorylation of signal transduction intermediates in
individual cells. When stimulated with cytokines, individual leukemia cells exhibit
marked differences in phosphoprotein patterns, which correspond with disease out-
come. Thus, single cell phosphoproteomic techniques are superior to other pro-
teomic technologies for the molecular diagnosis of disease and development of
personalized medicine. Although study of the phosphoprotein network is usually
associated with oncology, such a technology might be useful for other diseases for
which multiple treatment options exist and competing technologies have not been
able to adequately predict the optimal treatment for individual patients.
Diseases Due to Misfolding of Proteins
Taking on the right shape is vital to a protein’s action. To help make sure this hap-
pens correctly, cells contain chaperone proteins devoted to helping newly made pro-
teins fold. Other proteins, the ubiquitins, bind to proteins that have failed the shape
test and mark them for destruction.
Incorrectly folded proteins are at the root of several disorders. Prion diseases are
associated with misfolding of proteins and this is linked to the pathogenesis of neu-
rodegenerative disorders such as Alzheimer’s disease. Disturbance of protein fold-
ing system leads to spinocerebellar ataxia – a fatal movement disorder of childhood.
The gene mutation responsible for this disease is SCA1, which codes for a protein,
ataxin1. Mutations in the gene create an enlarged portion in ataxin1 containing
multiple copies of the amino acid glutamine. This stops the protein from folding
Diseases Due to Misfolding of Proteins