Welcome!

News Feed Item

Understanding and Improving the Body's Fight Against Pathogens

A*STAR scientists find new targets for modulating antibody response

Singapore, Sept 1, 2014 - (ACN Newswire) - Scientists from A*STAR's Bioprocessing Technology Institute (BTI) have uncovered the crucial role of two signalling molecules, DOK3 and SHP1, in the development and production of plasma cells. These discoveries, published in two prestigious journals PNAS and Nature Communications, advance the understanding of plasma cells and the antibody response, and may lead to optimisation of vaccine development and improved treatment for patients with autoimmune diseases such as lupus and tumours such as multiple myeloma[1].

While they exist in small populations in humans, the large amounts of antibodies secreted by plasma cells make them key to the body's immune system and its ability to defend itself against pathogens, such as bacteria and viruses. Proper maintenance of a pool of plasma cells is also critical for the establishment of lifelong immunity elicited by vaccination.

Dysregulation of plasma cell production and maintenance could lead to autoimmune diseases and multiple myeloma. Autoimmune diseases occur when the immune system does not distinguish between healthy tissue and antigens, which are found in pathogens. This results in expansion of plasma cells which produce excessive amounts of antibodies leading to destruction of one's own healthy tissue. The discoveries by scientists in BTI's Immunology Group have improved understanding of the mechanism by which plasma cells are developed from a major class of white blood cells called B cells.

For the first time, the molecule DOK3 was found to play an important role in formation of plasma cells. While calcium signalling typically controls a wide range of cellular processes that allow cells to adapt to changing environments, it was found to inhibit the expression of the membrane proteins essential for plasma cell formation. These membrane proteins include PDL1 and PDL2, and represent some of the key targets for the development of immunotherapy by pharmaceutical companies. DOK3 was able to promote the production of plasma cells by reducing the effects of calcium signalling on these membrane proteins. The absence of DOK3 would thus result in defective plasma cell formation.

In another study, BTI scientists discovered the importance of SHP1 signalling to the long term survival of plasma cells. While the molecule SHP1 has a proven role in prevention of autoimmune diseases, it was found that the absence of SHP1 would result in the failure of plasma cells to migrate from the spleen where they are generated to the bone marrow, a survival niche where they are able to survive for much longer periods. This could result in a reduction of the body's immune response and thus, an increased susceptibility to infections and diseases. The scientists in this study also successfully rectified the defective immune response caused by an absence of SHP1 by applying antibody injections, which might advance the development of therapeutics. On the other hand, targeting SHP1 might be a strategy to treat multiple myeloma where the accumulation of cancerous plasma cells in the bone marrow survival niches is undesirable.

Findings hold potential for improved treatment

The discovery of these new targets for modulating the antibody response allows the development of novel therapeutic strategies for patients with autoimmune diseases and cancer. Understanding the mechanism that governs plasma cell differentiation is also critical for the optimal design of vaccines and adjuvants, which are added to vaccines to boost the body's immune response.

Prof Lam Kong Peng, Executive Director of BTI, said, "These findings allow better understanding of plasma cells and their role in the immune system. The identification of these targets not only paves the way for development of therapeutics for those with autoimmune diseases and multiple myeloma, but also impacts the development of immunological agents for combating infections."

[1] Multiple myeloma is a cancer of plasma cells that causes bone debilitating diseases. It is considered to be incurable but treatable.

Notes to Editor:

The research findings described in this media release can be found in:

1. Proceedings of the National Academy of Sciences of the United States of America (PNAS) Journal, under the title, "Adaptor protein DOK3 promotes plasma cell differentiation by regulating the expression of programme cell death 1 ligands" by Xijun Ou,1, Shengli Xu,1,2, Yan-Feng Li,1, Kong Peng Lam,1,2,3,4

Full text of the PNAS paper can be accessed online from: http://www.pnas.org/content/early/2014/07/22/1400539111.abstract

2. Nature Communications Journal, under the title, "Shp1 signalling is required to establish the long-lived bone marrow plasma cell pool" by Yan-Feng Li,1, Shengli Xu,1,2, Xijun Ou,1, Kong Peng Lam,1,2,3,4.

1 Immunology Group, A*STAR Bioprocessing Technology Institute, Singapore
2 Department of Physiology, NUS Yong Loo Lin School of Medicine, Singapore
3 Department of Microbiology, NUS Yong Loo Lin School of Medicine, Singapore
4 Department of Pediatrics, NUS Yong Loo Lin School of Medicine, Singapore

Full text of the Nature Communications paper can be accessed online from: http://www.nature.com/ncomms/2014/140630/ncomms5273/full/ncomms5273.html

About the Bioprocessing Technology Institute (BTI)

Bioprocessing Technology Institute (BTI) is a member of the Agency for Science, Technology and Research (A*STAR). Established in 1990 as the Bioprocessing Technology Unit, it was renamed the Bioprocessing Technology Institute (BTI) in 2003. The research institute's mission is to develop manpower capabilities and establish cutting-edge technologies relevant to the bioprocessing community. Some of the key research areas include expression engineering, animal cell technology, stem cell research, microbial fermentation, downstream purification and analytics. For more information about BTI, please visit http://bti.a-star.edu.sg.

About A*STAR

The Agency for Science, Technology and Research (A*STAR) is Singapore's lead public sector agency that fosters world-class scientific research and talent to drive economic growth and transform Singapore into a vibrant knowledge-based and innovation driven economy. In line with its mission-oriented mandate, A*STAR spearheads research and development in fields that are essential to growing Singapore's manufacturing sector and catalysing new growth industries. A*STAR supports these economic clusters by providing intellectual, human and industrial capital to its partners in industry. A*STAR oversees 20 biomedical sciences and physical sciences and engineering research entities, located in Biopolis and Fusionopolis as well as their vicinity. These two R&D hubs, house a bustling and diverse community of local and international research scientists and engineers from A*STAR's research entities as well as a growing number of corporate laboratories. Please visit www.a-star.edu.sg .



Source: A*STAR

Contact:
Vanessa Loh
Senior Officer, Corporate Communications
Agency for Science, Technology and Research
Tel: +65 6826 6395
Email: [email protected]


Copyright 2014 ACN Newswire. All rights reserved. www.acnnewswire.com

More Stories By JCN Newswire

Copyright 2008 JCN Newswire. All rights reserved. Republication or redistribution of JCN Newswire content is expressly prohibited without the prior written consent of JCN Newswire. JCN Newswire shall not be liable for any errors or delays in the content, or for any actions taken in reliance thereon.

Latest Stories
Historically, some banking activities such as trading have been relying heavily on analytics and cutting edge algorithmic tools. The coming of age of powerful data analytics solutions combined with the development of intelligent algorithms have created new opportunities for financial institutions. In his session at 20th Cloud Expo, Sebastien Meunier, Head of Digital for North America at Chappuis Halder & Co., discussed how these tools can be leveraged to develop a lasting competitive advantage ...
WebRTC is the future of browser-to-browser communications, and continues to make inroads into the traditional, difficult, plug-in web communications world. The 6th WebRTC Summit continues our tradition of delivering the latest and greatest presentations within the world of WebRTC. Topics include voice calling, video chat, P2P file sharing, and use cases that have already leveraged the power and convenience of WebRTC.
"We're a cybersecurity firm that specializes in engineering security solutions both at the software and hardware level. Security cannot be an after-the-fact afterthought, which is what it's become," stated Richard Blech, Chief Executive Officer at Secure Channels, in this SYS-CON.tv interview at @ThingsExpo, held November 1-3, 2016, at the Santa Clara Convention Center in Santa Clara, CA.
In his session at 20th Cloud Expo, Mike Johnston, an infrastructure engineer at Supergiant.io, discussed how to use Kubernetes to set up a SaaS infrastructure for your business. Mike Johnston is an infrastructure engineer at Supergiant.io with over 12 years of experience designing, deploying, and maintaining server and workstation infrastructure at all scales. He has experience with brick and mortar data centers as well as cloud providers like Digital Ocean, Amazon Web Services, and Rackspace. H...
You know you need the cloud, but you’re hesitant to simply dump everything at Amazon since you know that not all workloads are suitable for cloud. You know that you want the kind of ease of use and scalability that you get with public cloud, but your applications are architected in a way that makes the public cloud a non-starter. You’re looking at private cloud solutions based on hyperconverged infrastructure, but you’re concerned with the limits inherent in those technologies.
All organizations that did not originate this moment have a pre-existing culture as well as legacy technology and processes that can be more or less amenable to DevOps implementation. That organizational culture is influenced by the personalities and management styles of Executive Management, the wider culture in which the organization is situated, and the personalities of key team members at all levels of the organization. This culture and entrenched interests usually throw a wrench in the work...
Most companies are adopting or evaluating container technology - Docker in particular - to speed up application deployment, drive down cost, ease management and make application delivery more flexible overall. As with most new architectures, this dream takes a lot of work to become a reality. Even when you do get your application componentized enough and packaged properly, there are still challenges for DevOps teams to making the shift to continuous delivery and achieving that reduction in cost ...
SYS-CON Events announced today that Massive Networks will exhibit at SYS-CON's 21st International Cloud Expo®, which will take place on Oct 31 – Nov 2, 2017, at the Santa Clara Convention Center in Santa Clara, CA. Massive Networks mission is simple. To help your business operate seamlessly with fast, reliable, and secure internet and network solutions. Improve your customer's experience with outstanding connections to your cloud.
DevOps is under attack because developers don’t want to mess with infrastructure. They will happily own their code into production, but want to use platforms instead of raw automation. That’s changing the landscape that we understand as DevOps with both architecture concepts (CloudNative) and process redefinition (SRE). Rob Hirschfeld’s recent work in Kubernetes operations has led to the conclusion that containers and related platforms have changed the way we should be thinking about DevOps and...
The question before companies today is not whether to become intelligent, it’s a question of how and how fast. The key is to adopt and deploy an intelligent application strategy while simultaneously preparing to scale that intelligence. In her session at 21st Cloud Expo, Sangeeta Chakraborty, Chief Customer Officer at Ayasdi, will provide a tactical framework to become a truly intelligent enterprise, including how to identify the right applications for AI, how to build a Center of Excellence to ...
Consumers increasingly expect their electronic "things" to be connected to smart phones, tablets and the Internet. When that thing happens to be a medical device, the risks and benefits of connectivity must be carefully weighed. Once the decision is made that connecting the device is beneficial, medical device manufacturers must design their products to maintain patient safety and prevent compromised personal health information in the face of cybersecurity threats. In his session at @ThingsExpo...
From 2013, NTT Communications has been providing cPaaS service, SkyWay. Its customer’s expectations for leveraging WebRTC technology are not only typical real-time communication use cases such as Web conference, remote education, but also IoT use cases such as remote camera monitoring, smart-glass, and robotic. Because of this, NTT Communications has numerous IoT business use-cases that its customers are developing on top of PaaS. WebRTC will lead IoT businesses to be more innovative and address...
Everything run by electricity will eventually be connected to the Internet. Get ahead of the Internet of Things revolution and join Akvelon expert and IoT industry leader, Sergey Grebnov, in his session at @ThingsExpo, for an educational dive into the world of managing your home, workplace and all the devices they contain with the power of machine-based AI and intelligent Bot services for a completely streamlined experience.
Because IoT devices are deployed in mission-critical environments more than ever before, it’s increasingly imperative they be truly smart. IoT sensors simply stockpiling data isn’t useful. IoT must be artificially and naturally intelligent in order to provide more value In his session at @ThingsExpo, John Crupi, Vice President and Engineering System Architect at Greenwave Systems, will discuss how IoT artificial intelligence (AI) can be carried out via edge analytics and machine learning techn...
FinTechs use the cloud to operate at the speed and scale of digital financial activity, but are often hindered by the complexity of managing security and compliance in the cloud. In his session at 20th Cloud Expo, Sesh Murthy, co-founder and CTO of Cloud Raxak, showed how proactive and automated cloud security enables FinTechs to leverage the cloud to achieve their business goals. Through business-driven cloud security, FinTechs can speed time-to-market, diminish risk and costs, maintain continu...