Corporate Banner
Satellite Banner
Genomics
Scientific Community
 
Become a Member | Sign in
Home>News>This Article
  News
Return

New Sensor Tracks Zinc in Cells

Published: Wednesday, December 11, 2013
Last Updated: Wednesday, December 11, 2013
Bookmark and Share
Shifts in zinc’s location could be exploited for early diagnosis of prostate cancer.

Zinc, an essential nutrient, is found in every tissue in the body. The vast majority of the metal ion is tightly bound to proteins, helping them to perform biological reactions. Tiny amounts of zinc, however, are only loosely bound, or “mobile,” and thought to be critical for proper function in organs such as the brain, pancreas, and prostate gland. Yet the exact roles the ion plays in biological systems are unknown.

A new optical sensor created at MIT tracks zinc within cells and should help researchers learn more about its functions. The sensor, which can be targeted to a specific organelle within the cell, fluoresces when it binds to zinc, allowing scientists to determine where the metal is concentrated.

The MIT chemists who designed the sensor have already used it to shed light on why zinc levels, normally high in the prostate, drop dramatically in cancerous prostate cells.

“We can use these tools to study zinc trafficking within prostate cells, both healthy and diseased. By doing so we’re trying to gain insight into how zinc levels within the cell change during the progression of prostate cancer,” says Robert Radford, an MIT postdoc who led the project and who is an author of the paper describing the sensors, which appears in the Dec. 9 issue of the Proceedings of the National Academy of Sciences.

Radford works in the lab of Stephen Lippard, the Arthur Amos Noyes Professor of Chemistry, a member of MIT's Koch Institute for Integrative Cancer Research, and senior author of the paper. The paper’s lead author is Wen Chyan, a 2013 MIT graduate.

Researchers in Lippard’s lab are now working on exploiting similar fluorescent sensors to develop a diagnostic test for early detection of prostate cancer, which is the second leading cause of cancer death in American men, but is considered very treatable if caught early enough.

Pathway to cancer

Among its known roles, zinc helps to stabilize protein structure and catalyzes some cellular reactions. In the prostate, zinc is believed to help with reproductive functions by aiding in the accumulation of citrate, a component of semen. Within mitochondria of epithelial prostate cells, zinc has been shown to inhibit the metabolic enzyme aconitase. By blocking the activity of aconitase, zinc truncates the citric acid cycle, the series of reactions that produce ATP, the cells’ major energy currency.

Scientists have theorized that when prostate cells become cancerous, they banish zinc from mitochondria (the cell structures where most ATP production occurs). This allows the cancer cell to produce the extra energy it needs to grow and divide.

“If a cell is dividing uncontrollably and it needs a lot of chemical energy, then it definitely wouldn’t want zinc interfering with aconitase and preventing production of more ATP,” Radford says.

The new MIT study supports this theory by showing that, although cancerous prostate cells can absorb zinc, the metal does not accumulate in the mitochondria, as it does in normal prostate cells.

This finding suggests that, in normal cells, zinc is probably transported into mitochondria by a specialized transport protein, but such a protein has not been identified, Radford says. In cancer cells, this protein might be inactivated.

Follow the zinc


The new zinc sensor relies on a molecule that Lippard’s lab first developed more than 10 years ago, known as Zinpyr1 (ZP1). ZP1 is based on a dye known as fluorescein, but it is modified to fluoresce only when it binds to zinc.

The ZP1 sensor can simply be added to a dish of cells grown in the lab, where it will diffuse into the cells. Until now, a major drawback of the sensor was the difficulty in targeting specific structures within a cell. “We have had some success using proteins and peptides to target small molecule zinc sensors,” Radford says, “but most of the time the sensors get captured in acidic vesicles within the cell and become inactive.”

Lippard’s team overcame that obstacle by making two changes: First, they installed a zinc-reactive protecting group, which altered the physical properties of the sensor and made it easier to target. Second, they attached an “address tag” that directs ZP1 into mitochondria. This tag, which is a derivative of triphenylphosphonium, is tailored to enter the mitochondria because it is both positively charged and hydrophobic. The resulting sensor readily entered cells and allowed the researchers to visualize pools of mobile zinc within mitochondria.

“This is an exciting new concept for sensing using a combination of reaction- and recognition-based approaches, which has potential applications for diagnostics involving zinc misregulation,” says Christopher Chang, a professor of chemistry and molecular and cell biology at the University of California at Berkeley who was not part of the research team.

In future studies, the researchers plan to expand their strategy to create a palette of sensors that target many other organelles in the cell.

“The identification of intracellular targets for mobile zinc is an important step in understanding its true function in biological signaling. The next steps will involve discovery of the specific biochemical pathways that are affected by zinc binding to receptors in the organelles, such as proteins, and elucidating the structural and attendant functional changes that occur in the process,” Lippard says.

The lab’s immediate interest is study of zinc in the brain, where it is believed to act as a neurotransmitter. By understanding mobile zinc in the auditory cortex, optic nerve, and olfactory bulb, the researchers hope to figure out its role in the senses of hearing, sight, and smell.


Further Information

Join For Free

Access to this exclusive content is for Technology Networks Premium members only.

Join Technology Networks Premium for free access to:

  • Exclusive articles
  • Presentations from international conferences
  • Over 3,300+ scientific posters on ePosters
  • More than 5,000+ scientific videos on LabTube
  • 35 community eNewsletters


Sign In



Forgotten your details? Click Here
If you are not a member you can join here

*Please note: By logging into TechnologyNetworks.com you agree to accept the use of cookies. To find out more about the cookies we use and how to delete them, see our privacy policy.

Related Content

Protecting Privacy in Genomic Databases
System helps ensure databases used in medical research will not leak patients’ personal information.
Wednesday, August 10, 2016
Triple-Action Therapy Patch Shows Promise
Patch that delivers drug, gene, and light-based therapy to tumor sites shows promising results in mice.
Wednesday, July 27, 2016
New Device can Study Electric Field Cancer Therapy
Microfluidic device allows study of electric field cancer therapy through low-intensity fields, preventing malignant cells spreading.
Friday, July 08, 2016
Illuminating Hidden Gene Regulators
New super-resolution technique visualizes important role of short-lived enzyme clusters.
Friday, May 27, 2016
A Programming Language for Living Cells
New language lets researchers design novel biological circuits.
Monday, April 04, 2016
Cancer Cells Remodel Environments Before Spreading
Researchers at MIT have found that the cancer cells remodel their environment to make it easier to reach nearby blood vessels.
Wednesday, March 16, 2016
Paving the Way for Metastasis
Cancer cells remodel their environment to make it easier to reach nearby blood vessels.
Tuesday, March 15, 2016
A New Way to Discover DNA Modifications
Researchers systematically find molecules that help regulate and protect DNA.
Wednesday, March 02, 2016
Mapping Regulatory Elements
Systematically searching DNA for regulatory elements indicates limits of previous thinking
Wednesday, February 03, 2016
Curing Disease by Repairing Faulty Genes
New delivery method boosts efficiency of CRISPR genome-editing system.
Wednesday, February 03, 2016
Supply Chain
Chemists discover how a single enzyme maintains a cell’s pool of DNA building blocks.
Wednesday, January 13, 2016
How Cancer Cells Spread
Study offers new targets for drugs that may prevent cancer from spreading.
Thursday, December 17, 2015
Scaling Up Synthetic-Biology Innovation
MIT professor’s startup makes synthesizing genes many times more cost effective.
Monday, December 14, 2015
Delivering microRNAs for Cancer Treatment
Scientists exploit gene therapy to shrink tumors in mice with an aggressive form of breast cancer.
Wednesday, December 09, 2015
CRISPR-Cas9 Genome Editing Hurdle Overcome
Team re-engineers system to dramatically cut down on editing errors; improvements advance future human applications.
Thursday, December 03, 2015
Scientific News
Gene Therapy Via Ultrasound
Research into a gene therapy approach called sonoporation could help combat heart disease and cancer.
Creating Embryos with 'Heteroplasmy'
New discovery in genetic research could lead to treatments for mitochondrial diseases.
Proteins Preserve Vital Genetic Data
Research has shown how two key proteins bring about the oragnization of chromosomes and our genome.
Novel MRI Technique Distinguishes Healthy Prostate Tissue from Cancer
The UTSW researchers have determined that glucose stimulates release of the zinc ions from inside epithelial cells, which they could then track on MRIs.
Eye Colour Determines Cancer Risk
Researchers report first findings of a link between eye pigment gene and uveal melanoma development.
Telomere Replenishment in Real Time
Researchers have visualised the process of telomere attachment to chromosomes through single-molecule imaging.
Converting Isolated Cells with Gene Editing
Researchers have used CRISPR to generate neuronal cells from isolated connective tissue.
New Inflammatory Disease Discovered
NIH researchers have discovered a rare and potentially deadly disease - otulipenia - the mostly affects children.
Gene Linked to Hearing Loss Identified
Researchers have identifed a gene associated with age-related hearing loss.
Oxygen Content Contributes to Cancer
Research project concludes lack of oxygen in tumour cells changes cell gene expression, contributing to the growth of cancer.
Skyscraper Banner

SELECTBIO Market Reports
Go to LabTube
Go to eposters
 
Access to the latest scientific news
Exclusive articles
Upload and share your posters on ePosters
Latest presentations and webinars
View a library of 1,800+ scientific and medical posters
3,300+ scientific and medical posters
A library of 2,500+ scientific videos on LabTube
5,000+ scientific videos
Close
Premium CrownJOIN TECHNOLOGY NETWORKS PREMIUM FOR FREE!