Research Round Up
Did Evolution Give Us Inflammatory Disease?
Philip De Jager, MD, PhD
Researchers demonstrate that some variants in our genes that contribute
to a person's risk for inflammatory diseases such as multiple sclerosis,
Crohn's disease or rheumatoid arthritis, have been the target of natural
selection over the course of human history.
The research team, led by Philip
De Jager, MD, PhD, of BWH's Department of Neurology, and Barbara
Stranger, PhD, of the University of Chicago, looked at genome-wide association
studies along with protein-protein interaction networks, as well as other data
and found 21 places in the genome that bear a ‘signature' for both inflammatory
disease susceptibility and natural selection.
Towfique Raj, PhD
Towfique Raj, PhD, of BWH's Department of Neurology, is the lead author
on this study. The study's findings suggest that, in the past, these variants
rose in frequency in the human population to help protect humans against
viruses, bacteria and other pathogens. But now in our modern world, the
environment and exposure to pathogens has changed, and the genetic variants
that were originally meant to protect us, now make an autoimmune reaction more
likely. These results are consistent with the hygiene hypothesis in which our
cleaner environment is thought to contribute to the increasing prevalence of
The study was published in the March 21, 2013 online issue of The American Journal of Human Genetics.
Protein-Protein Interactions Discovered Using Novel Method
Stephen Elledge, PhD
There are various methods that exist that help
characterize protein-binding molecules. Now
a BWH research team has added another
one to the list by developing a new approach, known as PLATO, for mapping physical
interactions between proteins and other molecules. PLATO, which stands for parallel
analysis of translated open reading frames, combines in vitro display of full-length proteins with analysis by
high-throughput DNA sequencing.
The research team, led by Stephen Elledge,
PhD, of the Division of Genetics in the Department of Medicine, used PLATO to
perform various interaction screens against a normalized collection of 15,483
human complementary DNA (a type of DNA involved in the formation of proteins).
and his team were able to identify proteins that interacted with LYN
kinase (an enzyme involved in cell activation), as well as small-molecules known
as gefitinib and dasatinib.
"PLATO adds a new tool to our arsenal of methods for identifying direct
interactions with proteins and should have a broad impact in drug target
discovery and antibody-antigen discovery," said Elledge.
The study was published in the March 17, 2013 online issue of Nature
Snx3 Protein Essential to Blood Cell Formation
Barry Paw, MD, PhD
A research team led by Barry Paw, MD, PhD, with Caiyong Chen, PhD, of
the BWH Division of Hematology, has found that a protein called Sorting Nexin 3
(Snx3), which is highly
expressed in vertebrate hematopoietic (blood-forming) tissues is essential in
red blood cell formation. Moreover, knocking out this protein's gene results in
anemia and hemoglobin defects in zebrafish embryos and mouse cells and tissues.
Caiyong Chen, PhD
The researchers observed that silencing of the Snx3 gene prevents the formation of the Snx3 protein which helps
transport and recycle the iron uptake machinery in red blood cells.
Furthermore, impairment of these processes leads to reduced assimilation and
utilization of iron by the red blood cells.
According to the researchers, having identified the mechanisms of Snx3 will
provide a genetic tool for further exploring red blood cell formation and iron
"The clinical significance of our work provides new areas of enhancing
the delivery of iron to red cells with iron deficiency," said Paw.
The study was published in the March 5, 2013 issue of Cell Metabolism.