Navigation Links
UMass Amherst researchers unravel secrets of parasites' replication

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
University of Massachusetts at Amherst

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:
Related Image:
UMass Amherst researchers unravel secrets of parasites' replication
(Date:11/27/2015)... (PRWEB) , ... November 27, 2015 , ... ... affecting the health care in America. As people age, more care is needed, ... costs are rising, and medical professionals are being overworked. The forgotten part of ...
(Date:11/27/2015)... ... 2015 , ... Lizzie’s Lice Pickers just announced a special promotion that will ... their purchase of lice treatment product. In addition, customers will receive a complimentary head ... “Finding lice is a sure way to ruin the holidays, so we encourage all ...
(Date:11/27/2015)... ... November 27, 2015 , ... Consistent with the ... 2016 Building Better Radiology Marketing Programs meeting will showcase some of the ... 2016, at Caesars Palace in Las Vegas with a pre-conference session on a ...
(Date:11/27/2015)... Bangalore, Karnataka (PRWEB) , ... November 27, 2015 ... ... the world, Health-E-minds, an innovative online platform for mental health and wellness consultation, ... KleverKid. , This partnership will bridge the knowledge gap experienced by parents and ...
(Date:11/27/2015)... California (PRWEB) , ... November 27, 2015 , ... Avid ... Joplin Ann Arbor Michigan boxing style concert posters. This is one of Joplin's most ... the Canterbury House at the University of Michigan in Ann Arbor. The According to ...
Breaking Medicine News(10 mins):
(Date:11/26/2015)... 3D bioprinting market is expected to reach ... by Grand View Research Inc. Rising prevalence of chronic diseases ... is expected to boost the market growth, as 3D bioprinting ... --> 3D bioprinting market is expected to reach ... by Grand View Research Inc. Rising prevalence of chronic diseases ...
(Date:11/26/2015)... 2015 ) ... "2016 Future Horizons and Growth Strategies in ... Supplier Shares, Country Segment Forecasts, Competitive Intelligence, ... --> ) has announced ... Horizons and Growth Strategies in the German ...
(Date:11/26/2015)... November 26, 2015 ... adds "Global Repaglinide Industry ... Report on China Repaglinide Market, 2010-2019" ... data and information to its online ... . --> ...
Breaking Medicine Technology: