Navigation Links
UMass Amherst researchers unravel secrets of parasites' replication
Date:7/10/2012

AMHERST, Mass. A group of diseases that kill millions of people each year can't be touched by antibiotics, and some treatment is so harsh the patient can't survive it. They're caused by parasites, and for decades researchers have searched for a "magic bullet" to kill them without harming the patient. Now, a team of microbiologists at the University of Massachusetts Amherst has made an advance that could one day lead to a new weapon for fighting parasitic diseases such as African sleeping sickness, chagas disease and leishmaniasis.

In the cover article of the current issue of Eukaryotic Cell, parasitologists Michele Klingbeil, doctoral candidate Jeniffer Concepcin-Acevedo and colleagues report the first detailed characterization of the way key proteins in the model parasite Trypanosoma brucei organize to replicate its mitochondrial DNA (mtDNA). Understanding this spatial and temporal coordination could mean a foot in the door to launch new attacks on one of the parasites' essential cell processes, Klingbeil says.

She adds, "Parasites such as T. brucei, which causes African sleeping sickness, are not straightforward to treat because they're too much like our own cells. Antibiotics are ineffective, so we treat them as invaders, with toxic chemicals. We are trying to find their weaknesses so we can exploit those and eventually develop a very selective, effective and acceptable treatment."

Advances have not come easily, in part because these parasites have the most complex mitochondrial genome structure in nature, say Klingbeil and Concepcin-Acevedo, the lead researcher on the project. To tackle it, they've focused on the trypanosome parasites' extremely complex method of mtDNA replication, which involves kinetoplast DNA or kDNA. Its core components are very unlike DNA replication in animals and human hosts, Klingbeil says, "so if we can inhibit the replication process and take away the kDNA, the parasites will die. That's one way we might be able to kill them."

Trypanosomes' kDNA is found as a nucleoid in the mitochondrion, where it holds many copies of catenated or networked minicircles and maxicircles that look like medieval chain mail under the microscope. These molecules pass information on to daughter cells via DNA polymerases whose job it is to copy all circles in the network. Trypanosomes have six mtDNA polymerases, while humans have just one.

To figure out how these trypanosomal polymerases know when to initiate DNA replication, Concepcin-Acevedo set up immunofluorescence experiments focused on tracking a particular one, known as mtDNA polymerase ID (POLID). By fluorescent labeling the POLID protein and tracking it over space and time, Concepcin-Acevedo quantified it and clarified its relationship to the overall replication process for the first time in a very discrete time window. The approach immediately paid off.

Klingbeil says, "As soon as Jeny began looking more closely at POLID localization she discovered a novel mechanism for how this protein participates in kDNA replication." In response to kDNA changes during the replication cycle, POLID was dynamically redistributing, or changing location, from the mitochondrial matrix to concentrated foci around the kDNA, and co-localizing with replicating kDNA molecules.

"This had been hypothesized, but never seen before," Klingbeil explains. It was amazing to witness. We visualized a mitochondrial replication protein undergoing dynamic localization for the first time, and linked it to DNA synthesis. No one had ever been able to do that in any mitochondrial DNA replication system before."

This important discovery explains how POLID engages in kDNA replication and opens up new avenues to study and intervene in mitochondrial protein dynamics, say the two parasitologists. Their ultimate success would be to find a chemical to inhibit POLID from carrying out its role during replication and target all parasites with kDNA structures.


'/>"/>

Contact: Janet Lathrop
jlathrop@admin.umass.edu
413-545-0444
University of Massachusetts at Amherst
Source:Eurekalert  

Related medicine news :

1. NIH awards $20 million over 5 years to train next generation of global health researchers
2. Researchers develop a new cell and animal model of inflammatory breast cancer
3. Researchers uncover a viable way for colorectal cancer patients to overcome drug resistance
4. Researchers Find Gene Mutations That May Be a Key to Autism
5. Researchers find evidence of banned antibiotics in poultry products
6. NJ stroke researchers report advances in spatial neglect research at AAN Conference
7. Autism by the numbers: Yale researchers examine impact of new diagnostic criteria
8. Researchers Map Brain Regions Linked to Intelligence
9. Researchers ID Genes That May Determine Mental Illness
10. Researchers Develop Blood Test for Depression
11. University of Cincinnati researchers win $3.7M grant from US Department of Defense
Post Your Comments:
*Name:
*Comment:
*Email:
Related Image:
UMass Amherst researchers unravel secrets of parasites' replication
(Date:12/8/2016)... ... December 08, 2016 , ... ... Medication Therapy Management (MTM), adherence, and other pharmacist-delivered patient care services, has announced ... counsel and Eric Hoessel to vice president of sales. , Litsinger joined ...
(Date:12/8/2016)... ... December 08, 2016 , ... Premier Fitness Camp (PFC) ... , the ultimate weight loss and wellness program, at their world headquarters of Omni ... provide immediate and long-term results to anyone seeking weight loss, personal development, a healthy ...
(Date:12/8/2016)... ... December 08, 2016 , ... STATEN ... been recognized for adherence to the highest standards of trauma, maternity, cancer and ... the center's president and CEO, Dr. Daniel Messina. , Among the recognitions, the ...
(Date:12/8/2016)... ... December 08, 2016 , ... ... Care Act. Dr. Botelho advocates for the mass media launching of story movements ... ongoing opportunities to share their unfortunate experiences; such a movement can generate the ...
(Date:12/8/2016)... ... December 08, 2016 , ... The Dan Carlisle Agency, ... Jefferson County, is announcing the launch of a charity drive to raise support ... homeless women and children in Birmingham has grown steadily since the 1980’s, and ...
Breaking Medicine News(10 mins):
(Date:12/9/2016)... Research and Markets has announced the addition of the ... ... forecasts the global optical transceiver market to grow at a CAGR ... covers the present scenario and the growth prospects of the global ... report considers the revenue generated from the shipment of optical transceivers ...
(Date:12/9/2016)... Dec. 9, 2016  RxWiki Inc., a digital health ... marketing strategies of thousands of pharmacies through its Digital ... Austin Inno,s "50 on Fire" Award in the ... pleased to accept the award as one of Austin,s ... Executive Officer at RxWiki. "Our platform gives independent retail ...
(Date:12/8/2016)... 2016 IRIDEX Corporation (NASDAQ: IRIX ) ... of common stock, $0.01 par value (the "Offering" with such ...  The final terms of the Offering will depend on market ... can be no assurance as to whether or when the ... the net proceeds it will receive from this offering for ...
Breaking Medicine Technology: