Protecting Beta Cells from the Immune System

A pancreatic beta cell. Image by Itkin-Ansari lab

 is caused by an overactive immune response that kills off insulin-producing beta cells. While beta cells can be transplanted to replace the ones that have been lost, the immune system will eventually kill those off as well.
For transplantation to be a viable treatment, the immune system must be controlled. Current transplant recipients take immunosuppressive drugs to prevent their  from attacking replacement presenting patients with a stark choice between diabetes and a suppressed immune system.
Sanford-Burnham adjunct assistant professor  is taking a different approach. Her laboratory has placed human pancreatic precursor cells in an immuno-protective device and transplanted them into mice. She was testing whether precursor cells will mature into productive beta cells in the body and whether the encapsulation device, made from a material akin to Gore-Tex, could prevent the immune system from attacking transplanted cells.

Spotlight on Disease: Type 1 Diabetes

A model of an insulin molecule. Though insulin is an effective treatment for diabetes, it is not a cure. Image courtesy of Wikimedia Commons.

Type 1 diabetes is an  – a person’s own immune system attacks found in the pancreas. Beta cells normally respond to high levels of sugar in the blood by releasing  a protein hormone that acts like a key binding to a lock (or receptor) that is present on every cell in the body. When insulin binds to its receptor, it unlocks a door in cells that allows this sugar—known as to enter and be used for energy.
Since type 1 diabetics lack insulin-producing beta cells, glucose remains in the blood and cells starve. Even with insulin therapy, the level of blood glucose in type 1 diabetics is not normal. Glucose is a highly reactive molecule that damages the cells and tissues that it contacts, particularly the cells that line blood vessels. As a result, diabetes is a leading cause of blindness, kidney disease, limb amputation and heart disease. Because type 1 diabetes commonly manifests in childhood, it has traditionally been called “juvenile” diabetes. Type 1 diabetes treatment is life-long; diabetics must carefully monitor their blood sugar and receive daily insulin injections or wear an insulin-delivering pump.

The Truth About AMPK

Researchers at Salk and Sanford-Burnham used tiny C. elegans to study AMPK and autophagy.

You may not be familiar with the protein  but if you exercise regularly, like to drink red wine, take certain diabetes medications or practice caloric restriction in hopes of extending your life, AMPK is very important to you. AMPK is a master switch that controls a number of key cellular mechanisms, and all the activities listed above stimulate AMPK signals.
Recently,  at the with assistance from at Sanford-Burnham, published a showing how AMPK triggers a process called  which recycles damaged parts when cells are low on energy. Problems with AMPK and autophagy are associated with type 2 diabetes, cancer, Alzheimer’s and other age-related diseases.

Crowdsourcing Science with TOPSAN

New advances in technology are allowing scientists to sequence genomes and determine the structures of the proteins they encode at a faster rate and lower cost than ever before. The  centers, such as the (JCSG), have been instrumental in establishing the structures of hundreds of proteins each year. While this flood of new data is a boon to science, the time and resources needed to analyze it all has become a major bottleneck.
“We have become victims of our own success,” explains  director of the Bioinformatics and Systems Biology program at Sanford-Burnham. “New protein structures are being determined all the time. And while it’s important to know what a protein looks like, we need to better leverage that information to improve our understanding of how a protein works and what biological functions it performs in a cell.” Moreover, knowledge of a protein’s structure and function is necessary for identifying its role in human health and disease, as well as unveiling its potential as a therapeutic target.
Several years ago, Dr. Godzik and his research team came up with an idea to protein structure annotation. In 2006, along with their JCSG colleagues, they launched (TOPSAN), a central portal for scientists to collect, share and distribute information about three-dimensional protein structures. TOPSAN embodies the idea that many can succeed where the individual cannot. No matter how much any one person knows about a particular protein, there are others in the scientific community who know more about other aspects of the same protein. Thus, the collective analyses from multiple experts around the world are far more informative than the localized information that any one individual – or even single research group – could contribute.

High-Impact Research

Dr. Sumit Chanda

Two years ago, Sanford-Burnham’s and colleagues collaborated on a aboutinfection. They were trying to figure out how the virus, with only nine genes that code for 15 proteins, could be so effective with such a small genetic payload. They knew the virus was hijacking human proteins to succeed, but they wanted to pinpoint exactly which proteins were affected. published October 3, 2008 in  identified 295 host proteins involved in HIV infection. Since then, these findings have greatly impacted HIV research. In recognition of the paper’s significance, Thomson Reutershas named it a paper for January 2011. In the  Drs. Chanda and Young said:

This was one of the first studies to combine genome-wide RNAi screening and bioinformatics to identify the repertoire of host cellular factors that help facilitate HIV replication in human cells. It represents a significant advance in our understanding of viral-host interactions, providing a blueprint of the machinery that is exploited by the virus.

The paper’s ripple effect is likely to continue - researchers are just now beginning to develop anti-HIV therapies that target some of these 295 host proteins.

DNA

Dr. Robert Rickert with Oxnard Foundation president Christopher Veitch

We are quite proud of the  Sanford-Burnham scientists have made in 2010. Their work has led to new insights into  and many other conditions. In addition to illuminating some of the fundamental mechanisms that cause disease, they have also worked to these findings into new therapies.
We would like to take this opportunity to thank our many supporters for helping us with this important work. Without you, we might not have the resources to pursue promising research.

DNA 101

In this image, cellular machinery (in yellow) is transcribing DNA (the chain on the right) into RNA (upper left). Illustration by Linda Nye

DNA is short for deoxyribonucleic acid. Two chains of four chemical bases (abbreviated A, T, C and G) make up DNA and act as a cell’s recipe book to make proteins. The particular sequence of a DNA chain – meaning the precise order of the four chemical bases – determines what will be made. A DNA segment beginning with ATTCGC would produce a very different protein than one that starts with CCGTAT. This can be likened to adjusting the order of letters in a word. Though the letters are the same, the meaning changes. For example,  act means something very different than cat.
Not all DNA is destined to become a protein. Just as a recipe might contain more information than just a list of ingredients, only some regions of your DNA – called  – are directly translated into proteins. Cellular machinery follows the instructions written in a gene’s recipe to create a corresponding sequence of   which is chemically similar to DNA but acts as a messenger, carrying the recipe from the . Out in the cell’s the mRNA sequence is read by more machines, called Following the mRNA instructions, ribosomes string together  the building blocks that make up proteins. Proteins do most of the work in the cell.
As  producing two cells where there was once only one, the parent cell’s DNA is duplicated and the same protein-making recipe is passed on to the daughter cell.