single cell genomics


Known for Medical Devices, 116 Yr Old BD Makes a Bold Move in Genomics

Talk to someone who attended this year’s AGBT, and you’ll know the big buzz was about single cell genomics. One of the exciting new platforms came from a new player in the genomics space and yet from a very old company.

Founded at the end of the 19th Century, Becton Dickinson (BD) has been one of America’s great medical device innovators. They made the first syringe designed specifically for insulin injections. Their BD Vacutainer became the standard for blood collection in the U.S. They designed the first “intelligent” insulin pump. At this year’s AGBT conference, BD showed up with a new genomics division announcing their new Resolve(TM) Single-Cell Analysis Platform.

Today we talk with the VP of BD Genomics, Stephen Gunstream. Stephen says life science researchers already know BD through the BD Biosciences unit which over the past thirty years has been perfecting flow cytometry for their single cell analyzers and sorters. Acknowledging that BD has been going through “a culture shift the past five to ten years,” Stephen says their history with flow cytometry made their recent move into single cell genomics tools a natural one.

“People talk about a resurgence in single cell genomics, but I wouldn’t really call it a resurgence,” says Stephen. "We’ve been analyzing cells for 30 years with flow cytometry. What has really changed is that the capabilities of next gen sequencing has allowed us to do this in a highly parallel manner at a cost which is a lot more affordable.”

So how will BD stand out in a rapidly maturing marketplace? What research does Stephen think the new platform will most impact? And perhaps most importantly, will BD with their century old history of experience with clinical products be able to significantly help guide genomics research products into the clinic?

Putting the Bench Next to the Bedside: Laurence Cooper, MD Anderson Cancer Center

Guests:

Laurence Cooper, MD, PhD, MD Anderson Cancer Center

Bio and Contact Info

Listen (4:55) When clinical science and bench research is one and the same

Listen (10:40) Single cell genomics enabling next level of immunotherapy

Listen (5:00) Marrying immunotherapy with gene therapy - Four clinical trials

Listen (4:18) Is this a new model for drug development?

Listen (8:30) Why has the war on cancer taken so long?

Laurence Cooper is one of those rare MD and PhD hybrids-what he calls a "'super nerd." Specializing in immunotherapy at MD Anderson Cancer Center, Dr. Cooper is a pediatric oncologist with a very important resource: he also runs a laboratory where he's able to study the basic biology underlining his patients' cancers.

"Clinical science and bench research are one and the same," he affirms in the interview.

This concept is nothing new. But that a doctor is able to treat his patients with therapy developed in his own laboratory is very rare.

Today's show with Dr. Cooper is the final program in our series on single cell genomics. He explains how the new tools for looking at and manipulating individual cells are transforming immunotherapy. Today, treatment for childhood leukemia has become much more targeted and way less toxic.

And Dr. Cooper is not limited only to naturally occurring stem cells in a donor to transplant to his patients. With genetic engineering, his lab is able to create or reengineer specific cell types for transplant. Currently the lab has four clinical trials going which enable Dr. Cooper and his team to treat his own patients with the latest therapies that are developed in the lab.

This marriage between the clinic and the lab is a powerful example of the translation of biomedical science. Could it be a model for drug development?

That depends a lot on funding, concedes Dr. Cooper. His lab is funded by MD Anderson, but also in large part through NIH grants. The interview ends with a discussion on funding for the "war on cancer" with a provocative comparison to the "war on terror."

On 9/11, 3,000 people died. Yet every two days, that many people die from cancer. Dr. Cooper wonders why "the outrage of 9/11 has not yet translated into outrage of still having 3,000 people die every two days."

We hope to have Dr. Cooper back on the program soon as part of our series on the "war on cancer."

Podcast brought to you by: Fluidigm - The leader in single-cell genomics and maker of the C1™ Single-Cell Auto Prep System. The path less traveled just got easier.

Alzheimer's a "National Emergency:" Larry Goldstein

Guests:

Larry Goldstein, PhD, Director, UCSD Stem Cell Program
Bio and Contact Info

Listen (2:50) Three stem cell projects

Listen (8:41) Single cell genomics some really cool technology

Listen (4:26) Alzheimer's will not be treated with a single drug

Listen (7:38) Alzheimer's a national emergency

Listen (2:59) Making a case for science funding

Listen (3:38) Thoughts about CIRM

Larry Goldstein came up quickly on the list for our series on Single Cell Genomics. Little did we know he would come on the show and make such a passionate case for biomedical research funding in general, and particularly for Alzheimer's. Early in the show Larry describes how he is using the "unbelievable, really cool technology" of single cell genomics in his lab. Director of UC San Diego's Stem Cell Program, Larry is using stem cells to study ALS (Lou Gehrig's Disease), Alzheimer's, and Neimann Pick Type C, a rare pediatric disease. Larry says that Alzheimer's has become a "national emergency."

"In the United States, the annual cost to the healthcare system of Alzheimer's disease is somewhere between $200 and $250 billion," he says in today's show. "The entire NIH appropriation is $30 billion." He goes on to point out that the amount of the NIH budget for Alzheimer's research--our only hope for alleviating the burden of the disease on the healthcare system--is $500 million. "The ratio of cost of research to cost of care is terrifying….This is insanity! We're bleeding money and doing next to nothing to stop the bleeding."

How is Larry making his case for Alzheimer's research and basic science in general? And what are his thoughts on CIRM (California Institute for Regenerative Medicine)? Goldstein is as eloquent a speaker as he is passionate.

A Great Time to Be in Biology: Steve Quake, Stanford

Podcast brought to you by: Ingenuity Variant Analysis - Identify causal variants from human sequencing data in just hours.

Guests:

Steve Quake, PhD, Professor, Bioengineering, Stanford
Bio and Contact Info

Listen (4:45) Bringing physics to biology

Listen (6:28) New technology driving the study of single cells

Listen (4:30) A great time to be in biology

Listen (4:32) Thoughts on privacy and incidental findings

Listen (4:05) What is holding back the adoption of genomic medicine?

Asked about how he comes up with so many inventions, today's guest, Steve Quake, replies that he is "impatient." It's a quick answer that leaves a lasting sting. Last year when Steve won the Lemelsen-MIT award for being such a mad-inventor, Jim Plummer, dean of the Stanford School of Engineering, wrote of Steve: “It is important to remember that, at just 43 years old, Steve Quake has introduced a number of inventions, any one of which most people would consider a lifetime achievement — and there’s more to come. The true measure of the man, however, is less in his remarkable productivity, but in the profound reach of his inventions".

Beginning with a discussion about the technology Steve developed and commercialized to drive the study of single cell genomics, our interview continues on into the realm of genomic medicine and and the future of biology. Is Steve a believer that we'll be living to 200 yrs old anytime soon? And what are his thoughts on the issue of incidental findings? Listen to Steve's latest ideas in today's program.

NOTE: Since this interview was taped, Steve was elected to the National Academy of Sciences. http://engineering.stanford.edu/research-profile/quake-elected-national-...

Garry Nolan: Trailblazing Single Cell Analysis

Podcast brought to you by: Fluidigm - The leader in single-cell genomics and maker of the C1™ Single-Cell Auto Prep System. The path less traveled just go easier.

Guests:

Garry Nolan, PhD, Professor of Microbiology and Immunology, Stanford University School of Medicine Bio and Contact Info

Listen (6:41) Why is the focus on the single cell so important?

Listen (5:18) Low hanging fruit from bulk analysis already picked

Listen (6:29) What has been the response to your work?

Listen (6:25) Commercializing work as diagnostics at Nodality

Listen (6:38) Biggest challenge is to simplify

Making a big decision several years ago that his lab would have the single focus on the single cell, Gary Nolan has become a global leader in a new discipline. In today's show, he shares his conviction that the next frontier in biology is to expand the number of parameters wherein the individual cell can be studied. "The low hanging fruit from bulk analysis has already been picked," he says. Gary is a founder of two companies, Rigel Pharma (publicly traded) and Nodality, wherein his research is being commercialized. Is 2013 the year of single cell genomics, we ask this trailblazer.

Democratizing Single Cell Genomics with Gajus Worthington, Fluidigm

Podcast brought to you by: Ingenuity Variant Analysis - Identify causal variants from human sequencing data in just hours.

Guest: Gajus Worthington, CEO, Fluidigm Bio and Contact Info

Chapters: (Advance the marker)

0:39 Looking at heterogeneity

6:18 How is your technology driving the study of single cells

13:35 Overcoming skepticism

18:29 The promise of IPS dependent on looking at cells separately

21:11 Single cell genomics will expand to every area of cell biology

25:31 Are you the next big Illumina?

30:01 BONUS: Chip holds as much plumbing as a one-thousand-room hotel

Gajus Worthington has a message. Molecular biologists have been studying the genetics of individual cells (single cell) for a long time. But the amount of manual labor required has been prohibitive to achieving sufficiently large data sets. Fluidigm, a tools company in South San Francisco, co-founded by Worthington, is changing that. Now a single micro fluidics chip that contains as much plumbing as a one-thousand-room hotel is driving the adoption of single cell genomics research. In today's interview, Worthington, also CEO of Fluidigm, explains the company's technology and some of its applications.

We've heard a lot lately about the heterogeneous nature of cancer tumors. But there is heterogeneity everywhere, including stem cells. "Some iPS (induced pluripotent stem) cells are more "gifted" than others," Worthington explains. "To make iPS achieve its promise, and the promise is amazing, you have to understand the mechanism by which these "gifted" cells go from one type to another." One assumes the company's name comes from the two words "fluidics" and "paradigm." Fluidigm's technology is enabling researchers to make a shift in paradigm necessary to go ever deeper into the complexity of biology. Will they be the next Illumina?

Highlights of the 5th Personalized Medicine World Conference

This week the always spectacularly organized Tal Behar and her team put on the 5th annual Personalized Medicine World Conference (#PMWCintl). I want to mention a couple highlights from the conference: prenatal diagnostics and cell profiling.

Prenatal Diagnostics

Tumor Heterogeneity and Personalized Medicine

My recent blog post, Tumor heterogeneity, revealed…, discussed the New England Journal of Medicine article by Gerlinger and colleagues describing the genetic heterogeneity found both within a patient’s individual tumor nodules and between spatially separate nodules. There has been a substantial amount of discussion of this work and angst about how it might signal the end of personalized medicine even before it really got started.



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