Featured Research

from universities, journals, and other organizations

Secrets of parasites' replication unraveled

Date:
July 10, 2012
Source:
University of Massachusetts at Amherst
Summary:
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 microbiologists report the first detailed characterization of the way key proteins in the model parasite Trypanosoma brucei organize to replicate its mitochondrial DNA.

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 Concepción-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 Concepción-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, Concepción-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, Concepción-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.

This work was funded by the National Institutes of Health's National Institute of Allergy and Infectious Diseases. Support for Concepción-Acevedo also came from NSF's Northeast Alliance for Graduate Education and the Professoriate program.


Story Source:

The above story is based on materials provided by University of Massachusetts at Amherst. Note: Materials may be edited for content and length.


Journal Reference:

  1. J. Concepcion-Acevedo, J. Luo, M. M. Klingbeil. Dynamic Localization of Trypanosoma brucei Mitochondrial DNA Polymerase ID. Eukaryotic Cell, 2012; 11 (7): 844 DOI: 10.1128/EC.05291-11

Cite This Page:

University of Massachusetts at Amherst. "Secrets of parasites' replication unraveled." ScienceDaily. ScienceDaily, 10 July 2012. <www.sciencedaily.com/releases/2012/07/120710141940.htm>.
University of Massachusetts at Amherst. (2012, July 10). Secrets of parasites' replication unraveled. ScienceDaily. Retrieved August 28, 2014 from www.sciencedaily.com/releases/2012/07/120710141940.htm
University of Massachusetts at Amherst. "Secrets of parasites' replication unraveled." ScienceDaily. www.sciencedaily.com/releases/2012/07/120710141940.htm (accessed August 28, 2014).

Share This




More Plants & Animals News

Thursday, August 28, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Super Healthful Fruits and Vegetables: Which Are Best?

Super Healthful Fruits and Vegetables: Which Are Best?

Ivanhoe (Aug. 27, 2014) — We all know that it is important to eat our fruits and vegetables but do you know which ones are the best for you? Video provided by Ivanhoe
Powered by NewsLook.com
Bad Memories Turn Good In Weird Mouse Brain Study

Bad Memories Turn Good In Weird Mouse Brain Study

Newsy (Aug. 27, 2014) — MIT researchers were able to change whether bad memories in mice made them anxious by flicking an emotional switch in the brain. Video provided by Newsy
Powered by NewsLook.com
Do Couples Who Smoke Weed Together Stay Together?

Do Couples Who Smoke Weed Together Stay Together?

Newsy (Aug. 27, 2014) — A study out of University at Buffalo claims couples who smoke marijuana are less likely to experience intimate partner violence. Video provided by Newsy
Powered by NewsLook.com
Panda Might Have Faked Pregnancy To Get Special Treatment

Panda Might Have Faked Pregnancy To Get Special Treatment

Newsy (Aug. 27, 2014) — A panda in China showed pregnancy symptoms that disappeared after two months of observation. One theory: Her pseudopregnancy was a ploy for perks. Video provided by Newsy
Powered by NewsLook.com

Search ScienceDaily

Number of stories in archives: 140,361

Find with keyword(s):
 
Enter a keyword or phrase to search ScienceDaily for related topics and research stories.

Save/Print:
Share:  

Breaking News:
from the past week

In Other News

... from NewsDaily.com

Science News

Health News

Environment News

Technology News



Save/Print:
Share:  

Free Subscriptions


Get the latest science news with ScienceDaily's free email newsletters, updated daily and weekly. Or view hourly updated newsfeeds in your RSS reader:

Get Social & Mobile


Keep up to date with the latest news from ScienceDaily via social networks and mobile apps:

Have Feedback?


Tell us what you think of ScienceDaily -- we welcome both positive and negative comments. Have any problems using the site? Questions?
Mobile iPhone Android Web
Follow Facebook Twitter Google+
Subscribe RSS Feeds Email Newsletters
Latest Headlines Health & Medicine Mind & Brain Space & Time Matter & Energy Computers & Math Plants & Animals Earth & Climate Fossils & Ruins