Navigation Links
Biology made simpler with clear tissues

In general, our knowledge of biologyand much of science in generalis limited by our ability to actually see things. Researchers who study developmental problems and disease, in particular, are often limited by their inability to look inside an organism to figure out exactly what went wrong and when.

Now, thanks to techniques developed at Caltech, scientists can see through tissues, organs, and even an entire body. The techniques offer new insight into the cell-by-cell makeup of organismsand the promise of novel diagnostic medical applications.

"Large volumes of tissue are not optically transparentyou can't see through them," says Viviana Gradinaru (BS '05), an assistant professor of biology at Caltech and the principal investigator whose team has developed the new techniques, which are explained in a paper appearing in the journal Cell. Lipids throughout cells provide structural support, but they also prevent light from passing through the cells. "So, if we need to see individual cells within a large volume of tissue"within a mouse kidney, for example, or a human tumor biopsy"we have to slice the tissue very thin, separately image each slice with a microscope, and put all of the images back together with a computer. It's a very time-consuming process and it is error prone, especially if you look to map long axons or sparse cell populations such as stem cells or tumor cells," she says.

The researchers came up with a way to circumvent this long process by making an organism's entire body clear, so that it can be peered throughin 3-Dusing standard optical methods such as confocal microscopy.

The new approach builds off a technique known as CLARITY that was previously developed by Gradinaru and her collaborators to create a transparent whole-brain specimen. With the CLARITY method, a rodent brain is infused with a solution of lipid-dissolving detergents and hydrogela water-based polymer gel that provides structural supportthus "clearing" the tissue but leaving its three-dimensional architecture intact for study.

The refined technique optimizes the CLARITY concept so that it can be used to clear other organs besides the brain, and even whole organisms. By making clever use of an organism's own network of blood vessels, Gradinaru and her colleaguesincluding scientific researcher Bin Yang and postdoctoral scholar Jennifer Treweek, coauthors on the papercan quickly deliver the lipid-dissolving hydrogel and chemical solution throughout the body.

Gradinaru and her colleagues have dubbed this new technique PARS, or perfusion-assisted agent release in situ.

Once an organ or whole body has been made transparent, standard microscopy techniques can be used to easily look through a thick mass of tissue to view single cells that are genetically marked with fluorescent proteins. Even without such genetically introduced fluorescent proteins, however, the PARS technique can be used to deliver stains and dyes to individual cell types of interest. When whole-body clearing is not necessary the method works just as well on individual organs by using a technique called PACT, short for passive clarity technique.

To find out if stripping the lipids from cells also removes other potential molecules of interestsuch as proteins, DNA, and RNAGradinaru and her team collaborated with Long Cai, an assistant professor of chemistry at Caltech, and his lab. The two groups found that strands of RNA are indeed still present and can be detected with single-molecule resolution in the cells of the transparent organisms.

The Cell paper focuses on the use of PACT and PARS as research tools for studying disease and development in research organisms. However, Gradinaru and her UCLA collaborator Rajan Kulkarni, have already found a diagnostic medical application for the methods. Using the techniques on a biopsy from a human skin tumor, the researchers were able to view the distribution of individual tumor cells within a tissue mass. In the future, Gradinaru says, the methods could be used in the clinic for the rapid detection of cancer cells in biopsy samples.

The ability to make an entire organism transparent while retaining its structural and genetic integrity has broad-ranging applications, Gradinaru says. For example, the neurons of the peripheral nervous system could be mapped throughout a whole body, as could the distribution of viruses, such as HIV, in an animal model.

Gradinaru also leads Caltech's Beckman Institute BIONIC center for optogenetics and tissue clearing and plans to offer training sessions to researchers interested in learning how to use PACT and PARS in their own labs.

"I think these new techniques are very practical for many fields in biology," she says. "When you can just look through an organism for the exact cells or fine axons you want to seewithout slicing and realigning individual sectionsit frees up the time of the researcher. That means there is more time to the answer big questions, rather than spending time on menial jobs."


Contact: Deborah Williams-Hedges
California Institute of Technology

Related biology news :

1. Recent advances in stem cell biology
2. Yeast meeting to showcase latest breakthroughs in genetics and molecular biology
3. International team sheds new light on biology underlying schizophrenia
4. Montreal hosts International Union of Microbiology Societies congresses
5. Marmoset sequence sheds new light on primate biology and evolution
6. Largest International Meeting for the Study of Reproductive Biology Attracts Researchers from 36 Countries in Grand Rapids, Michigan
7. New professorship in tissue engineering links molecular engineering, marine biology
8. Doctoral students to study biology, mechanics connection under NIH grant
9. Biology of infection: A bacterial ballistic system
10. UMD-led public computational biology web service gains popularity
11. An ecological risk research agenda for synthetic biology
Post Your Comments:
Related Image:
Biology made simpler with clear tissues
(Date:10/29/2015)... , Oct. 29, 2015 Daon, a global ... it has released a new version of its ... North America have already installed ... also includes a FIDO UAF certified server component ... preparing to activate FIDO features. These customers include some ...
(Date:10/29/2015)... BOSTON , Oct. 29, 2015  Connected health ... phenomena driving the explosion of technology-enabled health and wellness, ... his new book, The Internet of Healthy ... apps, sensors or smartphones even existed, Dr. Kvedar, vice ... model of health care delivery, moving care from the ...
(Date:10/29/2015)... 29, 2015 Today, LifeBEAM , ... with 2XU, a global leader in technical performance ... hat with advanced bio-sensing technology. The hat will ... monitor key biometrics to improve overall training performance. ... two companies will bring together the most advanced technology, ...
Breaking Biology News(10 mins):
(Date:11/24/2015)... 2015 --> ... "Oligonucleotide Synthesis Market by Product & Services (Primer, Probe, ... DNA, RNAi), End-User (Research, Pharmaceutical & Biotech, Diagnostic Labs) ... market is expected to reach USD 1,918.6 Million by ... CAGR of 10.1% during the forecast period. ...
(Date:11/24/2015)... ... ... The Academy of Model Aeronautics (AMA), led by its Executive Council, has officially ... to represent the First–Person View (FPV) racing community. , FPV racing has exploded in ... racing and several new model aviation pilots have joined the community because of their ...
(Date:11/24/2015)... , November 24, 2015 ... market research report released by Transparency Market Research, the ... at a CAGR of 17.5% during the period between ... Market - Global Industry Analysis, Size, Volume, Share, Growth, ... non-invasive prenatal testing market to reach a valuation of ...
(Date:11/24/2015)... , Nov. 24, 2015 /PRNewswire/ - Aeterna Zentaris ... today that the remaining 11,000 post-share consolidation (or ... Warrants (the "Series B Warrants") subject to the ... on November 23, 2015, which will result in ... giving effect to the issuance of such shares, ...
Breaking Biology Technology: