Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:


UMass Amherst Researchers Unravel Secrets of Parasites’ Replication

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.

Link to Eukaryotic Cell cover story:

Janet Lathrop | EurekAlert!
Further information:

More articles from Life Sciences:

nachricht Gene therapy shows promise for treating Niemann-Pick disease type C1
27.10.2016 | NIH/National Human Genome Research Institute

nachricht 'Neighbor maps' reveal the genome's 3-D shape
27.10.2016 | International School of Advanced Studies (SISSA)

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Etching Microstructures with Lasers

Ultrafast lasers have introduced new possibilities in engraving ultrafine structures, and scientists are now also investigating how to use them to etch microstructures into thin glass. There are possible applications in analytics (lab on a chip) and especially in electronics and the consumer sector, where great interest has been shown.

This new method was born of a surprising phenomenon: irradiating glass in a particular way with an ultrafast laser has the effect of making the glass up to a...

Im Focus: Light-driven atomic rotations excite magnetic waves

Terahertz excitation of selected crystal vibrations leads to an effective magnetic field that drives coherent spin motion

Controlling functional properties by light is one of the grand goals in modern condensed matter physics and materials science. A new study now demonstrates how...

Im Focus: New 3-D wiring technique brings scalable quantum computers closer to reality

Researchers from the Institute for Quantum Computing (IQC) at the University of Waterloo led the development of a new extensible wiring technique capable of controlling superconducting quantum bits, representing a significant step towards to the realization of a scalable quantum computer.

"The quantum socket is a wiring method that uses three-dimensional wires based on spring-loaded pins to address individual qubits," said Jeremy Béjanin, a PhD...

Im Focus: Scientists develop a semiconductor nanocomposite material that moves in response to light

In a paper in Scientific Reports, a research team at Worcester Polytechnic Institute describes a novel light-activated phenomenon that could become the basis for applications as diverse as microscopic robotic grippers and more efficient solar cells.

A research team at Worcester Polytechnic Institute (WPI) has developed a revolutionary, light-activated semiconductor nanocomposite material that can be used...

Im Focus: Diamonds aren't forever: Sandia, Harvard team create first quantum computer bridge

By forcefully embedding two silicon atoms in a diamond matrix, Sandia researchers have demonstrated for the first time on a single chip all the components needed to create a quantum bridge to link quantum computers together.

"People have already built small quantum computers," says Sandia researcher Ryan Camacho. "Maybe the first useful one won't be a single giant quantum computer...

All Focus news of the innovation-report >>>



Event News

#IC2S2: When Social Science meets Computer Science - GESIS will host the IC2S2 conference 2017

14.10.2016 | Event News

Agricultural Trade Developments and Potentials in Central Asia and the South Caucasus

14.10.2016 | Event News

World Health Summit – Day Three: A Call to Action

12.10.2016 | Event News

Latest News

How nanoscience will improve our health and lives in the coming years

27.10.2016 | Materials Sciences

OU-led team discovers rare, newborn tri-star system using ALMA

27.10.2016 | Physics and Astronomy

'Neighbor maps' reveal the genome's 3-D shape

27.10.2016 | Life Sciences

More VideoLinks >>>