The Salk Institute has hired two new faculty members, bringing expertise in immunology and mitochondrial function.

* Susan Kaech will become director of the Norris Center for Immunobiology and Microbial Pathogenesis.

* Gerald Shadel will join Salks Molecular and Cell Biology Laboratory.

Kaech studies how immune cells called T cells remember previous infections, so they can respond more quickly to the same infection. Shes also studied how cancer suppresses the immune response.

Shadel specializes in the roles of mitochondrial dysfunction in aging and disease. Mitochondria are cellular organelles that contain their own DNA and are best known as the cells energy producers. Unhealthy mitochondria are a factor in Alzheimers and Parkinsons diseases, as well as cardiovascular ailments.

Both currently at Yale University, they are scheduled to arrive in early 2018. While married to each other, Kaech and Shadel conduct their research independently.

Kaechs research has won her awards including the Howard Hughes Medical Institute Early Career Scientist award, the Presidential Early Career Award for Scientists and Engineers, the Edward Mallinckrodt Jr. award and the Burroughs-Wellcome Foundation award.

Kaech and Shadel said they were attracted to the Salk Institute not only because of its reputation as a center of basic research, but by the scientific community in San Diego as a whole.

The scientific community is very welcoming and warm and scientifically interactive, Kaech said.

Moreover, the scientific community participates in the larger San Diego community, taking part in activities such as educational outreach, fundraising and philanthropy.

It seems to be a little bit more vibrant in the San Diego community than what I've experienced before, Kaech said.

Likewise, the nonscientific community is interested in what San Diego scientists are doing.

So that's another kind of attraction, (the interest) seems a little bit more communitywide, Kaech said. Science is clearly on the minds of people in San Diego.

The Salk Institute itself exemplifies this collaborative spirit, Kaech said.

Great minds are there, all interacting together, she said. How they cross-fertilize each other's research is very exciting, for me to be a part of that.

Shadels honors include an Amgen Outstanding Investigator award, the Glenn Foundations Glenn Award for Research in Biological Mechanisms of Aging and the Glenn/AFAR Breakthroughs in Gerontology Award.

Shadel said being located at the Salk Institute will put him in a better position to study the multiple functions of mitochondria, in part by interdisciplinary research with other experts.

I think my lab has been instrumental, along with others, to show that mitochondria are integrated into cells for other reasons in addition to the energetic functions, Shadel said.

What really excited me about the Salk was this chance to interact with really great experts in other fields and bring my research to the interface with other disciplines and really answer questions in bold new ways.

I also knew several of the people who were professors there already who are involved in the aging research realm mostly, but also others are involved in metabolism as well.

What this leads to is the power of fundamental science to help solve some of societys most pressing problems, Shadel said.

In my opinion, the most transformative types of discoveries are born out of pure basic research endeavors, and the Salk Institute has a really rich history of groundbreaking basic science, he said.

bradley.fikes@sduniontribune.com

(619) 293-1020

UPDATES:

The Salk Institute has hired two new faculty members, bringing expertise in immunology and mitochondrial function. Both from Yale University, they are scheduled to arrive in early 2018 with the rank of full professor.

-- Susan Kaech will become director of the Norris Center for Immunobiology and Microbial Pathogenesis. She studies how immune cells called T cells remember previous infections, enabling them to mobilize more rapidly to subsequent exposure.

-- Gerald Shadel will join the Salks Molecular and Cell Biology Laboratory. He is noted for research on the role of mitochondrial dysfunction in aging and disease. Mitochondria are organelles that contain their own DNA.

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Salk Institute hires two noted researchers - The San Diego Union-Tribune

June 30, 2017 Researchers have found a way to tweak cells' movement patterns to resemble those of other cell types. Credit: Tim Phelps/Johns Hopkins University

Johns Hopkins researchers report they have uncovered a mechanism in amoebae that rapidly changes the way cells migrate by resetting their sensitivity to the naturally occurring internal signaling events that drive such movement. The finding, described in a report published online March 28 in Nature Cell Biology, demonstrates that the migratory behavior of cells may be less "hard-wired" than previously thought, the researchers say, and advances the future possibility of finding ways to manipulate and control some deadly forms of cell migration, including cancer metastasis.

"In different tissues inside the body, cells adopt different ways to migrate, based on their genetic profile and environment," says Yuchuan Miao, a graduate student at the Johns Hopkins University School of Medicine and lead author of the study. "This gives them better efficiency to perform specific tasks." For example, white blood cells rhythmically extend small protrusions that allow them to squeeze through blood vessels, whereas skin cells glide, like moving "fans," to close wounds.

On the other hand, Miao notes, uncontrolled cell migration contributes to diseases, including cancer and atherosclerosis, the two leading causes of death in the United States. The migration of tumor cells to distant sites in the body, or metastasis, is what kills most cancer patients, and defective white blood cell migration causes atherosclerosis and inflammatory diseases, such as arthritis, which affects 54 million Americans and costs more than $125 billion annually in medical expenditures and lost earnings.

Because cells migrate in different ways, many drugs already designed to prevent migration work only narrowly and are rarely more than mildly effective, fueling the search for new strategies to control migratory switches and treat migration-related diseases, according to senior author Peter Devreotes, Ph.D., a professor and director of the Department of Cell Biology at the Johns Hopkins University School of Medicine's Institute for Basic Biomedical Research.

"People have thought that cells are typed by the way they look and migrate; our work shows that we can change the cell's migrating mode within minutes," adds Devreotes.

For the new study, Devreotes and his team focused on how chemical signaling molecules activate the motility machinery to generate protrusions, cellular "feet" that are a first step in migration. To do this, they engineered a strain of Dictyostelium discoideum, an amoeba that can move itself around in a manner similar to white blood cells. The engineered amoebae responded to the chemical rapamycin by rapidly moving the enzyme Inp54p to the cell surface, where it disrupted the signaling network. The cells also contained fluorescent proteins, or "markers," that lit up and showed researchers when and where signaling molecules were at work.

Experiments showed that the engineered cells changed their migration behavior within minutes of Inp54p recruitment. Some cells, which the researchers termed "oscillators," first extended protrusions all around the cell margins and then suddenly pulled them back again, moving in short spurts before repeating the cycle. Fluorescent markers showed that these cycles corresponded to alternating periods of total activation and inactivation, in contrast to the small bursts of activity seen in normal cells.

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Other cells began to glide as "fans," with a broad zone of protrusions marked by persistent signaling activity.

Devreotes describes the signaling behavior at the cell surface as a series of waves of activated signaling molecules that switch on the cellular motility machinery as they spread. In their normal state, cells spontaneously initiated signaling events to form short-lived waves that made small protrusions.

In contrast, oscillators had faster signaling waves that reached the entire cell boundary to generate protrusions before dying out. Fans also showed expanded waves that continually activated the cell front without ever reaching the cell rear, resulting in wide, persistent protrusions.

The scientists say their experiments show that the cell movement changes they saw resulted from lowering the threshold level of signaling activity required to form a wave. That is, cells with a lower threshold are more likely to generate waves and, once initiated, the activation signals spread farther with each step.

Devreotes says the team's experimental results offer what appears to be the first direct evidence that waves of signaling molecules drive migratory behavior. Previously, his laboratory showed a link between signaling and migration, but had not specifically examined waves.

In further experiments, Devreotes and his team found that they could recruit different proteins to shift cell motility, suggesting, he says, that altering threshold is a general cell property that can change behaviorno matter how cells migrate. His team was also able to restore normal motility to fans and oscillators by blocking various signaling activities, suggesting new targets for drugs that could be designed to control migration.

Devreotes cautions that what happens in an amoeba may not have an exact counterpart in a human cell, but studies in his lab suggest that something like the wave-signaling mechanism they uncovered operates in human cells as well.

The bottom line, says Miao, is that "we now know we can change signaling wave behavior to control the types of protrusions cells make. When cells have different protrusions, they have different migratory modes. When we come to understand the essential differences between cells' migratory modes, we should have better ways to control them during disease conditions."

Explore further: How cells communicate to move together as a group

More information: Yuchuan Miao et al. Altering the threshold of an excitable signal transduction network changes cell migratory modes, Nature Cell Biology (2017). DOI: 10.1038/ncb3495

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Scientists manipulate 'signaling' molecules to control cell migration - Phys.Org

Scientists canstudy only the things that we can observe. We are limited to studying natural, detectable phenomena.

In the history of biology, bursts of discoveries often follow breakthroughs in technology.

The first microscopes in the 1590s permitted discovery of cells and microbes in the 1600s. Biologists described the tenets of modern cell theory by the 1850s. All organisms are made of cells. Cells are the basic unit of living things. Cells are produced by other cells.

After World War II, the 1946 Atomic Energy Act permitted the U.S. government to sell radioactive isotopes, produced in nuclear reactors, for research and medical treatments. Using these atomic energy byproducts, biologists identified DNA as the genetic material in 1952. They described the structure of DNA in 1953, and explained how DNA replicates in 1958.

Those dominoes of DNA discovery that began falling in the middle of the last century led to the release of the complete human genome sequence at the start of this century. Along the way, we invented technologies to automate gene sequencing. And what started as a slow, laborious, expensive process has become a rapid, easy, inexpensive way to map every gene of any organism thata biologist studies.

At the start of the DNA age, biologists identified a species of interest and acquired a specimen. They then extracted, sequenced and compared its genes with other species.

Modern, automated gene sequencing reverses this process.

With high-throughput DNA sequencers, biologists identify all of the genes in a sample of ocean water or human gut contents. They use computer programs to assemble the most likely community of microorganisms in the sample. They use gene sequences to identify species present in a microbiome, all of the microbes in the sample.

Invention of microscopes led to the discovery of cells and microorganisms. Invention of high-throughput gene sequencing techniques has led to the discovery of microbiomes around us, on us and in us.

Biologists have just begun to discover the extent and impact of microbiomes. Consider these microbiome discoveries published in the past two months:

Pregnant mothers with decreased vaginal microbiome diversity experience more preterm births.

Characterizing the gut microbiome of patients with inflammatory bowel disease can advise effective therapies to treat the condition.

Patients with an imbalanced gut microbiome are more likely to have scleroderma, an autoimmune disease that hardens and scars connective tissue.

Composition of a persons microbiome might influence his or her risk for obesity and nonalcoholic fatty liver disease. Characterization of the gut microbiome might provide early warning of the disease.

Composition of the microbiome in hair follicles might influence the development of acne in patients.

What you dont see, you cant understand. As individual organisms, we are living ecological communities with healthy and diverse or not microbiomes on us and in us. We interact with and depend on individuals of other species to feed us and provide us other ecological services. Each of those individuals has a microbiome.

You cant tell the players without a program. Were in the earliest stages of writing programs to identify players in microbiomes on which we depend.

Steve Rissing is a biology professor at Ohio State University.

steverissing@hotmail.com

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Biology: Technological advances help us understand the world in and around us - The Columbus Dispatch

Leukemia researchers led by Dr. John Dick have traced the origins of relapse in acute myeloid leukemia (AML) to rare therapy-resistant leukemia stem cells that are already present at diagnosis and before chemotherapy begins.

They have also identified two distinct stem-cell like populations from which relapse can arise in different patients in this aggressive cancer that they previously showed starts in blood stem cells in the bone marrow.

The findings provide significant insights into cell types fated to relapse and can help accelerate the quest for new, upfront therapies, says Dr. Dick, a Senior Scientist at Princess Margaret Cancer Centre, University Health Network, and Professor in the Department of Molecular Genetics, University of Toronto. He holds the Canada Research Chair in Stem Cell Biology and is Co-leader of the Acute Leukemia Translational Research Initiative at the Ontario Institute for Cancer Research. This study was primarily undertaken by post-doctoral fellow Dr. Liran Shlush and Scientific Associate Dr. Amanda Mitchell.

"For the first time, we have married together knowledge of stem cell biology and genetics areas that historically have often been operating as separate camps to identify mutations stem cells carry and how they are related to one another in AML," says Dr. Dick, who pioneered the cancer stem cell field by identifying leukemia stem cells in 1994.

A decade ago, he replicated the entire human leukemia disease process by introducing oncogenes into normal human blood cells, transplanting them into xenografts (special immune-deficient mice that accept human grafts) and watching leukemia develop a motherlode discovery that has guided leukemia research ever since.

The researchers set out to solve the mystery of AML relapse by analysing paired patient samples of blood taken at the initial clinic visit and blood taken post-treatment when disease recurred.

"First, we asked what are the similarities and differences between these samples. We carried out detailed genetic studies and used whole genome sequencing to look at every part of the DNA at diagnosis, and every part of the DNA at relapse," says Dr. Dick. "Next, we asked in which cells are genetic changes occurring."

The two-part approach netted a set of mutations seen only at relapse that enabled the team to sift and sort leukemic and normal stem cells using tools developed in the Dick lab a few years ago to zero in on specific cell types fated to relapse.

"This is a story that couldn't have happened five years ago, but with the evolution of deep sequencing, we were able to use the technology at just the right time and harness it with what we've been working on for decades," he says.

Today's findings augment recent research also published in Nature (Dec.7, 2016) detailing the team's development of a "stemness biomarker" a 17-gene signature derived from leukemia stem cells that can predict at diagnosis which AML patients will respond to standard treatment.

Dr. Dick says: "Our new findings add to that knowledge and we hope that we will soon have a new biomarker that will tell whether a patient will respond to standard chemotherapy, and then another to track patients in remission to identify those where treatment failed and the rare leukemia stem cells are coming back.

"These new kinds of biomarkers will lead to new kinds of clinical trials with targeted chemotherapy. Right now, everybody gets one size fits all because in AML we've never had any opportunity to identify patients upfront, only after they relapse. Now we have the first step to identify these patients at the outset and during remission."

The research was funded by the Ontario Institute for Cancer Research, the Cancer Stem Cell Consortium via Genome Canada and the Ontario Genomics Institute, the Canadian Institutes of Health Research, the Canadian Cancer Society, the Terry Fox Foundation, a Canada Research Chair and The Princess Margaret Cancer Foundation.

This article has been republished frommaterialsprovided byUHN. Note: material may have been edited for length and content. For further information, please contact the cited source.

Reference:

Shlush, L. I., Mitchell, A., Heisler, L., Abelson, S., Ng, S. W., Trotman-Grant, A., . . . Dick, J. E. (2017). Tracing the origins of relapse in acute myeloid leukaemia to stem cells. Nature. doi:10.1038/nature22993

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Stem Cells Play a Role in Acute Myeloid Leukemia Relapse - Technology Networks