The Michigan Daily - michigandaily.com
Monday, March 19, 2012 - 5A
The Michigan Daily - michigandailycomMonday, March 19, 2012 - 5A
Research team analyzes
impact of Hsp33 protein
Findings recently
published in
prominent science
publication
By ANNA ROZENBERG
Daily Staff Reporter
Chaperones aren't just the
awkward adults at your high-
school dance, but also a type of
protein that University faculty
are starting to better scientifi-
cally understand.
Biology Prof. Ursula Jakob
and a team of collaborators
comprise a study that exam-
ines chaperone protein Hsp33,
which the team specifically
investigated in bacteria. The
study has been going on over
the course of the past four
years, and they recently had
their paper published in Cell, a
renowned biology journal.
The function of chaperone
proteins is to help other pro-
teins function, and until Jakob's
study, the way in which Hsp33
work in bacteria was unknown.
She said the implications for
studies on such proteins are cru-
cially important, since all mod-
ern life relies on the function of
proteins to carry out basic pro-
cesses in cells to survive.
Jakob said when any cell in
any organism encounters stress-
es like a fever or viral infection,
its proteins start to denature,
or lose the structure that they
need to function properly.
"Not only do they lose activ-
ity, but what's worse, they start
to want to form aggregates,"
Jakob said. "This is very toxic
for the cell. The reason it's so
toxic is it's irreversible."
Jakob said this conglomera-
tion is similar to an egg boil-
ing, beginning in a liquid form
before turning solid through
the boiling process. Jakob and
her team discovered how Hsp33
prevents protein inside bacte-
ria cells from hardening when
under attack by stressors, spe-
cifically bleach.
"This is important because
we produce bleach in our body,"
Jakob said. "Our white blood
cells produce bleach to kill off
bacteria."
Jakob and her team found
that when bleach activates
Hsp33, it actually unfolds, los-
ing some of its structure before
interacting with other proteins.
"In contrast to all the other
proteins which unfold and lose
their function, Hsp33 needs
this unfolding to gain its func-
tion," Jakob said. "This is very
contrary to what has been in
the textbooks for many, many
years."
Until this study, it was a well-
known theory that proteins lose
function when they lose their
structure, according to Jakob.
However, because Hsp33 does
the opposite, the new find-
ings seem to be a revolutionary
exception to the rule, she said.
"(Hsp33) uses the flexibility
it gets because it loses part of
its structure to really embrace
and mold itself around other
proteins that are unfolding
and thus preventing them from
interacting with other unfold-
ing proteins and forming those
aggregates," Jakob said.
Jakob explained that the sec-
ond part of the study involved
discovering what happens once
the stressor is gone, and how
the partially unfolded proteins
regain their structure so they
can again perform functions
required for the bacteria to live.
"Ideally, the client needs to
gain back its structure to func-
tion again, because we want to
survive the stress condition, not
just endure it," Jakob said.
Jakob and her team found
that when the stressful condi-
tions dissipate, Hsp33 pulls the
client protein farther apart.
This conformational change
allows the client protein to be
available for another class of
chaperone proteins that will
refold them to their active state,
according to Jakob.
"In general, it's a mechanism
for how bacteria defend them-
selves against stress - stress
that they encounter when they
invade us," Jakob said. "It's a
very clever strategy these bac-
teria have developed because
it's so instantaneous."
Though chaperone proteins
like Hsp33 are found mainly
in bacteria, they also appear in
some unicellular, eukaryotic
parasites like Trypanosoma
that causes sleeping sickness,
Jakob said. Ultimately, she said
her team hopes to use their
findings for drug design against
such diseases.
"If we understand how they
defend themselves, we can
understand how to attack them
better," she said.
Dana Reichmann, research
fellow in the Department of
Biology and another author of
the paper, further explained the
significance of the discoveries
regarding Hsp33.
"We knew it's important for
bacteria, but we didn't really
know the mechanism for the
protection," Reichmann said.
Reichmann said Hsp33 acts
like Play-Doh in its flexibility,
binding to the proteins at risk
from stress in order to protect
them.
"There is really nice struc-
tural interplay with the chaper-
ones and the substrate ... They
affect the conformation of each
other which enables further
release of the protein," Reich-
mann said.
Reichmann also highlighted
that before their research, it
was unclear how Hsp33 acted
without any added Adenyl tri-
phosphate energy - the prima-
ry energy source produced and
used by the human body.
"It's really one of the first
chaperones which are not
ATP-dependent chaperones,"
Reichmann said. "Up to now, it
was unclear how these types of
chaperones were working ... it
brings another mechanism to
different types of chaperones,
not necessarily the ones we
know."
Reichmann said there are
homologous proteins found in
plants, and more studies relat-
ing to Hsp33 and similar chap-
erone proteins are in the works,
noting that this study is just the
beginning.
"To look at chaperones and
parasites and look at how we
can target them ... this will be
MATCH DAY
From Page1A
ebrate the hard work and success
of the students.
"As a faculty member, we take
great pride in the opportunity to
mold and help launch the careers
in medicine of these talented
young men and women," Wool-
liscroft said.
A ceremony filled with mixed
emotions of joy, relief and hys-
teria followed the lunch ban-
quet during which each student
shared their placement on stage.
Rajesh Mangrulkar, associate
dean for medical student educa-
tion, said he finds it very exciting
to see students embark on the
next stage of their professional
career.
"It's also a day that many of
our students choose to share
with those who have supported
them - their family, friends,
and our faculty and staff," Man-
grulkar said. "So Match Day feels
like a community comingtogeth-
er to celebrate this important
step for them."
Mangrulkar said when he was
a medical student, Match Day
was a mixture of relief, nervous
anticipation and exuberance.
"For the first time, they will be
practicing physicians in the field
they have chosen - and nowthey
know where that will be," Man-
grulkar said.
Mangrulkar added that the
day was very dramatic for many
of the students who will be mov-
ing to a brand new city with a
new medical culture.
"Imagine not knowing where
you are going to live one minute,
and then opening up an envelope
and knowing exactly where you
have to live," Mangrulkar said.
Mangrulkar reminded stu-
dents that the profession will
provide numerous challenges in
theirthree to sevenyear residen-
cy placements.
"Our patients really need
change agents to go out and
improve their health, through
clinical care, research and edu-
cation," Mangrulkar said. "Build
on your wonderful foundation
from U-M, and never forget why
you went into medicine in the
first place."
Medical student Hela Issaq,
who received the Harold Kes-
sler, M.D. Scholarship award in
December 2011 for her commit-
ment to the principles of fam-
ily medicine, said she is thrilled
about receiving residency train-
ing in the Department of Fam-
ily Medicine at Harbor-UCLA in
Harbor City, CA.
"I was emotional because I
had thought about this day for
the past four years and it was
finally here," Issaq said. "I knew
that I wanted to do family medi-
cine even before I started medi-
cal school and my dream was
coming true."
Issaq added that she is also
elated to be the first female
Afghan-American medical stu-
dent to graduate from the Uni-
versity's medical school.
Medical student Ian May said
in some respects, the name of the
hospital placed inside the small
white envelope represents the
sum of an individual's medical
achievements thus far.
"I had a jumble of feelings,
excitement, foreboding, ner-
vousness all rolled into one,"
May said. "In hindsight, it seems
a little strange that such a thing
could produce such a combina-
tion of anxiety and elation."
May will spend his residency
training for emergency medicine
at Madigan Army Medical Cen-
ter in Tacoma, Wash.
A tradition of the University's
Match Day includes students
using pins to pinpoint their
placement site on a map of the
United States.
Medical student Eric Tannen-
baumplacedhispinonAnnArbor
as his residence in orthopedic
surgery will be at the University
of Michigan Health System.
"My first choice was Michi-
gan. When I opened the envelope
and got Michigan as my match, it
felt as ifa 50 pound weight was
lifted off my chest," Tannen-
baum said.
He added that he was nervous
about where he and his fiancae
would be spending their lives for
the next five years. Upon discov-
ering he was placed in Ann Arbor,
he said it was the first moment he
was able to truly relax as a medi-
cal student.
While29 percentofgraduating
students will remain at the Uni-
versity for their residency, other
graduates were placed at institu-
tions in 22 states acrossthe coun-
try, including Washington D.C.,
California and New York, accord-
ingto a UMHS release.
The release also indicated that
99 percent of graduating medi-
cal students were able to obtain
a placementthis year, puttingthe
University 5 percent above the
national average.
The placements were deter-
mined by the National Resident
Matching Program, a not-for-
profit corporation thatuses auni-
formed process to place 16,000
medical students at residency
sites each year.
Each placement site submits
a list of applicants in the order
of preference and each appli-
cant will also rank his or her site
preferences. Then, a computer
program will compare the lists
against each other and deter-
mine the most appropriate place-
ment.
FOLLOW THE DAILY ON
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@MIC H IGANDAILY
one of tne nest in tne nation.
Every year, U-M students form
S the largest share of our entering
Doctor of Pharmacy (PharmD)
class. Their undergraduate
majors range from biology and chemistry to psy-
chology and anthropology; international studies
and sociology to English and engineering.
25 Years Back, 25 Years Forward:
Environmental Law At The Crossroads
March 23-24, 2012
University of Michigan Law School,
Hutchins and South Hall, Ann Arbor, MI
KEYNOTE SPEAKER
Friday, March 23, 12:45 P.M.
Bob Perciasepe
Deputy Administrator, U.S. Environmental Protection Agency
FEATURED SPEAKERS
Friday, March 23, 9:00 A.M.
Richard Lazarus
Howard and Katherine Abel Professor of Law, Harvard Law School
Saturday, March 24, 12:00 P.M.
John Cruden