YSM Issue 86.3

INFECTIOUS DISEASES
body of the infected tsetse fly.
One of Tschudi’s colleagues,
Serap Aksoy, possesses one of
the two tsetse fly colonies in the
United States, and the research
group infected and dissected a
sample of these flies to determine
the biological progression
of the infection. Upon realizing
that RBP6, an RNA-binding
protein, increased by a factor of
13 during the middle stage of the
infectious process, Tschudi and
his colleagues decided to replicate
this observation in vitro. Their initial goal
was hardly to replicate the infectious process,
but simply to study the binding protein. They
induced overexpression of RBP6 to determine
which type of RNA is bound by the protein.
Ten days later, they came upon unexpected
results: the cultured, non-infectious cells had
become infectious cells.
“When I told my colleague George Cross at
Rockefeller University, he was speechless. Then
he finally said, ‘This is the biggest thing that
has happened in the last 20 years,’” Tschudi
recalled. He went on to explain that the fact
“that one single protein can trigger these events
is close to unheard of, not just in the trypanosome
field, but just science in general.” Considering
that the trypanosome genome encodes
around 10,000 proteins, the importance of the
single protein RBP6 is truly striking.
Stopping the Next Domino
IMAGE COURTESY OF GEOFFREY ATTARDO
The tsetse fly can kill people and livestock
in Africa by infecting them with
sleeping sickness.
The replication of the infection process
through the overexpression of RBP6 shed a bit
of light on the stage of the parasite’s life cycle
that has been called the “heart of darkness.” He
explained that this stage transpires as a domino
effect with many potential points of intervention.
In the ten days between the overexpression
and the infection, T. brucei undergoes a
IMAGES COURTESY OF CHRISTIAN TSCHUDI
T. bruce in its infectious state (left) and its non-infectious state (right).
variety of complicated transformations including
a change in physical shape and a silencing of
previously active mitochondria. To understand
the how of the infectious process — how these
transformations are related, and how they ultimately
lead to infection — each domino in the
chain must be studied individually.
Tschudi’s group is in search for a more effective
target point of intervention than the overexpression
of RBP6. He believes that although
the overexpression triggers a sequence of
events that certainly lead to infection, the
RBP6 protein is not directly involved in the
infection. Looking forward, Tschudi hopes
to discover what the overexpression of RBP6
subsequently triggers. “What happens after 24
hours? What changes in the cell? We try to look
at everything globally, analyzing around 5,000
of the 10,000 proteins that technology allows
for,” he explained.
With only two tsetse fly colonies possessed
by U.S. laboratories and the relatively low attention
the disease receives in the medical world,
collaboration is necessary in the trypanosome
field. Tschudi, who came to Yale over thirty
years ago, said that African sleeping sickness
is a neglected tropical disease, as it does not
receive the same level of attention as other
deadly tropical diseases such as malaria. “We
welcome others and have already started collaborations
with people. The more we work on
it, the faster the field moves forward.”
Hopefully, Tschudi’s discovery will help alleviate
some of the negative impacts that sleeping
sickness has wrought. The deaths of human
beings, at around 50,000 per year, is only a part
of the problem caused by African sleeping sickness.
Nagana, the deadly livestock version of
the sleeping sickness, actually has an enormous
economic impact on Sub-Saharan countries.
Tschudi hopes that one day, reduced cases of
nagana will help the economic development of
the impoverished Sub-Saharan African region.
Finding the right domino to remove from the
chain of infection would signify a victory not
only for individuals infected with the disease,
but also against the poverty it perpetuates in
affected regions.
About the Author
Stephany Seung Yeon Rhee is a freshman in Saybrook College and an Electrical
Engineering and Computer Science major. She is the Multimedia Editor for the
Yale Scientific.
Acknowledgements
The author would like to thank Professor Christian Tschudi for his time and enthusiasm
about his discovery.
Further Reading
• Kolev, Nikolay G., K. Ramey-Butler, G. A. M. Cross, E. Ulllu, C. Tschudi. 2012.
“Developmental Progression to Infectivity in Trypanosoma brucei Triggered by an
RNA-Binding Protein.” Science, December 7.
www.yalescientific.org April 2013 | Yale Scientific Magazine 13