Navigation Links
La Jolla Institute discovers new player critical to unleashing T cells against disease

SAN DIEGO (June 23, 2013) A major study from researchers at the La Jolla Institute for Allergy and Immunology provides new revelations about the intricate pathways involved in turning on T cells, the body's most important disease-fighting cells, and was published today in the prestigious scientific journal Nature.

The La Jolla Institute team is the first to prove that a certain type of protein, called septins, play a critical role in activating a calcium channel on the surface of the T cell. The channel is the portal through which calcium enters T cells from the blood stream, an action essential for the T cell's survival, activation, and ability to fight disease.

Patrick Hogan and Anjana Rao, Ph.D.s, are senior authors on the paper and Sonia Sharma and Ariel Quintana, Ph.D.s, are co-first authors. Drs. Sharma, Rao and Hogan are former researchers at Harvard Medical School with high-level genetics expertise who joined the La Jolla Institute in 2010. Dr. Quintana conducted advanced microscopy that was a major aspect of the study.

Dr. Hogan describes the discovery as another important step in understanding the overall functioning of T cells knowledge from which new, more precisely targeted drugs to treat diseases ranging from cancer to viral infections can emerge. "It's like working on an engine, you have to know what all the parts are doing to repair it," he says. "We want to understand the basic machinery inside a T cell. This will enable us to target the specific pressure points to turn up a T cell response against a tumor or virus or to turn it down in the case of autoimmune diseases."

The findings were published in a Nature paper entitled "An siRNA screen for NFAT activation identifies septins as coordinators of store-operated Ca2+ entry."

"We have found that the septin protein is a very strong regulator of the calcium response, which is essential for activating immune cells," says Dr. Sharma, who was recently appointed to a faculty position, and now leads her own independent laboratory at the La Jolla Institute, in addition to serving as scientific director of the newly established RNAi screening center.

Dr. Hogan says the discovery took the research team by surprise. "We knew septins existed in the cellular plasma (surface) membrane, but we didn't know they had anything to do with calcium signaling," he says. Septins are known to build scaffolding to provide structural support during cell division.

This finding builds on Dr. Rao and Dr. Hogan's groundbreaking discovery in 2006 showing that the protein ORAI1 forms the pore of the calcium channel. The channel's entryway had been one of the most sought after mysteries in biomedical science because it is the gateway to T cell functioning and, consequently, to better understanding how the body uses these cells to fight disease.

To the research team's surprise, the septins were forming a ring around the calcium channel. "We aren't sure why, but we theorize that the septins are rearranging the cellular membrane's structure to "corral" the key proteins STIM and ORAI1, and maybe other factors needed for the calcium channel to operate," says Dr. Hogan.

Dr. Sharma adds that, "essentially we believe the septins are choreographing the interaction of these two proteins that are important in instigating the immune response." Without the septins' involvement, T cell activation does not occur.

In the study, the researchers devised a simple visual readout of activity in a main pathway responsible for activation of T cells the same pathway that is targeted by the immunosuppressive drug cyclosporin A that is used clinically and looked for impairment of the activity when individual genes were, in effect, deleted. After sorting through the roughly 20,000 human genes, they turned up 887 gene "hits," says Dr. Hogan.

With further experiments, they should be able to classify those hits into genes that affect the calcium channel itself and genes that act later in the pathway. "We are hopeful that one or more of these genes can be used as a clinical target for new drugs to treat transplant rejection and immune diseases, some of the same indications now treated with cyclosporine A," adds Dr. Hogan. He believes that a medication aimed at an early step of calcium entry through the ORAI channel could be more effective and have fewer side effects than cyclosporin A, which targets a later step in the pathway and can cause complications such as kidney disease.


Contact: Bonnie Ward
La Jolla Institute for Allergy and Immunology

Related biology news :

1. La Jolla Institute identifies molecular switch enabling immune cells to better fight disease
2. La Jolla institute identifies critical cell in fighting E. coli infection
3. La Jolla Institute scientist discovers key step in immune system-fueled inflammation
4. La Jolla Institute discovery could lead to new way to screen drugs for adverse reactions
5. National Institutes of Health to fund research probing proteins linked to cancer, diabetes
6. Roy J. Carver Charitable Trust funds new research focus at Institute for Genomic Biology
7. The DOE Joint Genome Institute expands capabilities via new partnerships
8. St. Jude scientist named Howard Hughes Medical Institute investigator
9. Feinstein Institute collaborates with GSK, UPenn, MIT to research bodys electrical impulses
10. DOE Joint Genome Institute 8th Annual Meeting on March 26-28, 2013
11. Forsyth Institute receives $4.1 million grant for new center
Post Your Comments:
(Date:11/9/2015)... Calif. , Nov. 9, 2015  Synaptics Inc. ... interface solutions, today announced broader entry into the automotive ... solutions that match the pace of consumer electronics human ... biometric sensors are ideal for the automotive industry and ... Europe , ...
(Date:10/29/2015)... Va. , Oct. 29, 2015 Daon, ... today that it has released a new version of ... customers in North America have ... IdentityX v4.0 also includes a FIDO UAF certified ... are already preparing to activate FIDO features. These customers ...
(Date:10/27/2015)... -- In the present market scenario, security is one ... verticals such as banking, healthcare, defense, electronic gadgets, and ... secure & simplified access control and growing rate of ... bank accounts, misuse of users, , and so on. ... and smartphones are expected to provide potential opportunities for ...
Breaking Biology News(10 mins):
(Date:11/24/2015)... -- Clintrax Global, Inc., a worldwide provider of clinical research services headquartered ... the company has set a new quarterly earnings record in Q3 ... posted for Q3 of 2014 to Q3 of 2015.   ... , with the establishment of an Asia-Pacific ... United Kingdom and Mexico , with ...
(Date:11/24/2015)... ... November 24, 2015 , ... This fall, global software solutions leader SAP ... states to develop and pitch their BIG ideas to improve health and wellness in ... for votes to win the title of SAP's Teen Innovator, an all-expenses paid trip ...
(Date:11/24/2015)... , November 24, 2015 SHPG ) announced ... in the Piper Jaffray 27 th Annual Healthcare Conference in ... 1, 2015, at 8:30 a.m. EST (1:30 p.m. GMT). --> ... Financial Officer, will participate in the Piper Jaffray 27 th ... NY on Tuesday, December 1, 2015, at 8:30 a.m. EST (1:30 ...
(Date:11/24/2015)... , Nov. 24, 2015  Tikcro Technologies Ltd. (OTCQB: TIKRF) today ... December 29, 2015 at 11:00 a.m. Israel time, ... Tower, 98 Yigal Allon Street, 36 th Floor, Tel ... Eric Paneth and Izhak Tamir to the Board ... Skaliter as external directors; , approval of an amendment to certain ...
Breaking Biology Technology: