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

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
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 2,600+ scientific posters on ePosters
  • More than 3,800+ 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 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

Viruses Join Fight Against Harmful Bacteria
Engineered viruses could combat human disease and improve food safety.
Friday, September 25, 2015
Targeting DNA
Protein-based sensor could detect viral infection or kill cancer cells.
Tuesday, September 22, 2015
Targeting DNA
Protein-based sensor could detect viral infection or kill cancer cells.
Tuesday, September 22, 2015
Searching Big Data Faster
Theoretical analysis could expand applications of accelerated searching in biology, other fields.
Thursday, August 27, 2015
A Metabolic Master Switch Underlying Human Obesity
Researchers find pathway that controls metabolism by prompting fat cells to store or burn fat.
Friday, August 21, 2015
Identifying a Key Growth Factor in Cell Proliferation
Researchers discover that aspartate is a limiter of cell proliferation.
Friday, July 31, 2015
Firms “Under-invest” in Long-Term Cancer Research
Tweaks to the R&D pipeline could create new drugs and greater social benefit.
Thursday, July 30, 2015
Nanoparticles Can Clean Up Environmental Pollutants
Researchers have found that nanomaterials and UV light can “trap” chemicals for easy removal from soil and water.
Thursday, July 23, 2015
Researchers Develop Genetic Tools to Engineer Common Gut Bacterium
Researchers from the Massachusetts Institute of Technology have developed genetic parts that can be combined to program the commensal gut bacterium Bacteroides thetaiotaomicron.
Friday, July 10, 2015
Longstanding Problem Put to Rest
Proof that a 40-year-old algorithm for comparing genomes is the best possible will come as a relief to computer scientists.
Thursday, June 11, 2015
Diagnosing Cancer with Help from Bacteria
Engineered probiotics can detect tumors in the liver.
Friday, May 29, 2015
Master Gene Regulator Could Be New Target For Schizophrenia Treatment
Researchers at MIT’s Picower Institute for Learning and Memory have identified a master genetic regulator that could account for faulty brain functions that contribute to schizophrenia.
Wednesday, May 27, 2015
Brain Tumor Weakness Identified
Discovery could offer a new target for treatment of glioblastoma.
Thursday, April 09, 2015
New Nanodevice Defeats Drug Resistance
Tiny particles embedded in gel can turn off drug-resistance genes, then release cancer drugs.
Wednesday, March 04, 2015
New Nanodevice Defeats Drug Resistance
Tiny particles embedded in gel can turn off drug-resistance genes, then release cancer drugs.
Tuesday, March 03, 2015
Scientific News
Genes That Protect African Children From Developing Malaria Identified
Variations in DNA at a specific location on the genome that protect African children from developing severe malaria, in some cases nearly halving a child’s chance of developing the life-threatening disease, have been identified in the largest genetic association study of malaria to date.
Researchers Disguise Drugs As Platelets to Target Cancer
Researchers have for the first time developed a technique that coats anticancer drugs in membranes made from a patient’s own platelets.
Dormant Viral Genes May Awaken to Cause ALS
NIH human and mouse study may open an unexplored path for finding treatments.
Scientists Create World’s Largest Catalog of Human Genomic Variation
An international team of scientists from the 1000 Genomes Project Consortium has created the world’s largest catalog of genomic differences among humans, providing researchers with powerful clues to help them establish why some people are susceptible to various diseases.
Five Genetic Regions Implicated In Cystic Fibrosis Severity
An international consortium of researchers conducted the largest-ever CF genome-wide analysis to find new therapeutic targets.
Greater Understanding Of Polycystic Ovary Syndrome
A new genetic study of over 200,000 women reveals the underlying mechanisms of polycystic ovary syndrome, as well as potential interventions.
New Autism Genes Are Revealed in Largest-Ever Study
Work draws more detailed picture of genetic risk, sheds light on sex differences in diagnosis.
A Fundamental Protection Mechanism Against Formalin In Mammals is Revealed
Formaldehyde, or formalin, is well known to all of us as a common chemical used in many industrial processes and also as a preservative, remarkably we also produce formaldehyde in our bodies.
A New Single-Molecule Tool to Observe Enzymes at Work
A team of scientists at the University of Washington and the biotechnology company Illumina have created an innovative tool to directly detect the delicate, single-molecule interactions between DNA and enzymatic proteins.
Genetic Adaptations to Diet and Climate
Researchers found genetic variations in the Inuit of Greenland that reflect adaptations to their specific diet and climate.
Skyscraper Banner

Skyscraper Banner
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
2,600+ scientific and medical posters
A library of 2,500+ scientific videos on LabTube
3,800+ scientific videos