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Genetics, In the News, Medicine and Society, Research

James Watson to put Nobel medal on the auction block

James Watson to put Nobel medal on the auction block

DNA Template molecular modelLooking for the perfect holiday gift for the science geek in your life? Have an extra $3 million sitting around? If so, you can bid on James Watson’s Nobel Medal, which will be auctioned off by Christie’s on December 4 and is expected to fetch between $2.5 and $3.5 million. Watson, now 86, won the Nobel Prize in Physiology or Medicine in 1962 for deciphering the structure of DNA, along with Francis Crick and Maurice Wilkins. An article in Reuters noted the significance of the medal’s auction and the 1953 finding for which it was awarded:

“It is recognition of probably the most significant scientific breakthrough of the 20th century and the impact of it is only being played out now in the 21st century,” said Francis Wahlgren, international head of books and manuscripts at Christie’s. “Whole industries have developed around it.”

Countless subsequent scientific discoveries in the last half century have their foundation in Watson and Crick’s work. Last year, Francis Crick’s Nobel medal garnered $2.27 million. Watson’s handwritten notes for his acceptance speech will also be auctioned the same day. He plans to donate part of the proceeds from the sales to charities and to scientific research.

Previously: Coming soon: A genome test that costs less than a new pair of shoes, NPR explores the pros and cons of scientists sequencing their own genes, and Image of the Week: Watson and Crick
Photo of thymine template from Watson and Crick’s 1953 molecular model by Science Museum London

Biomed Bites, Genetics, Research, Stem Cells, Videos

Working on a gene therapy for muscular dystrophy

Working on a gene therapy for muscular dystrophy

Here’s this week’s Biomed Bites, a weekly feature that highlights some of Stanford’s most innovative research and introduces Scope readers to innovators in a variety of biomedical disciplines. 

The most common form of muscular dystrophy, Duchenne muscular dystrophy, is genetic, resulting from a defective gene on the X chromosome, so it affects primarily boys. That makes it a prime target for genetic therapy – currently the goal of Stanford geneticist Michele Calos, PhD.

Calos started out as a basic scientist, examining the nature of DNA and the controls of genes; they developed techniques used to insert new genes into existing cells and ensure they are turned on.

Now, Calos has found applications for her earlier research. Capitalizing on the work that won the 2012 Nobel Prize in Medicine, Calos and her team have set their sights on developing healthy muscle cells that can restore function for muscular dystrophy patients. Here’s Carlos in the video above:

We’re repairing the mutation in the patients’ cells… then putting back the correct copy of the gene, differentiating them into muscle precursors and injecting them into muscles where they can form healthy muscle fibers.

Calos said she and her team are currently perfecting the technique in mice, before it can be used in human patients. “Our dream really is to develop a therapy in the lab that would be translatable to clinical use in the future,” she said.

Learn more about Stanford Medicine’s Biomedical Innovation Initiative and about other faculty leaders who are driving biomedical innovation here.

Previously: Elderly muscle stem cells from mice rejuvenated by Stanford scientists, New mouse model for muscular dystrophy provides clues to cardiac failure and Visible symptoms: Muscular-dystrophy mouse model’s muscles glow like fireflies as they break down

Genetics, NIH, Research, Science, Stanford News, Technology

Of mice and men: Stanford researchers compare mammals’ genomes to aid human clinical research

Of mice and men: Stanford researchers compare mammals' genomes to aid human clinical research

Scientists have long considered the laboratory mouse one of the best stand-ins for researching human disease because of the animals’ genetic similarity to humans. Now Stanford researchers, as part of a consortium of more than 30 institutions, have confirmed the mouse’s utility in clinical research by showing that the basic principles controlling genes are similar between the two species. However, they also found some important differences.

From our press release on the work:

“At the end of the day, a lot of the genes are identical between a mouse and a human, but we would argue how they’re regulated is quite different,” said Michael Snyder, PhD, professor and chair of genetics at Stanford. “We are interested in what makes a mouse a mouse and a human a human.”

The research effort, Mouse ENCODE, complements a project called the Encyclopedia of DNA Elements, or ENCODE, both funded by the National Human Genome Research Institute. ENCODE studied specific components in the human genome that guide genes to code for proteins that carry out a cell’s function, a process known as gene expression. Surrounding the protein-coding genes are noncoding regulatory elements, molecules that regulate gene expression by attaching proteins, called transcription factors, to specific regions of DNA.

The Mouse ENCODE consortium annotated the regulatory elements of the mouse genome to make comparisons between the two species. Because many clinical studies and drug discovery use mice as model organisms, understanding the similarities and differences in gene regulation can help researchers understand whether their mouse study applies to humans.

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Aging, Genetics, In the News, Research, Stanford News

“A lot more data” needed to determine what makes supercentenarians live so long

"A lot more data" needed to determine what makes supercentenarians live so long

Scientists from Stanford and elsewhere have been hunting for a genetic explanation for extreme longevity for the past four years and are realizing that it is a more difficult proposition than they initially hoped.

Their research compared the genomes of 17 “supercentenarians” – those who have lived 110 years and beyond – with those of 4,300 “regular” people recorded earlier in a National Institutes of Health study. The study was geared toward finding a single gene or group of genes responsible for a particular trait – in this case longevity – similar to genes which have been found to cause disease or confer immunity. But they have had no luck. Stuart Kim, PhD, a Stanford geneticist and molecular biologist and founder of the Kim Lab for the study of aging, commented in a San Francisco Chronicle piece:

We were looking for a really simple explanation in a single gene, and we know now that it’s a lot more complicated, and it will take a lot more experiments and a lot more data from the genes of more supercentenarians to find out just what might account for their ages.

However, data about the oldest people in the world still suggests that the reason they can live so long has to do with their genes, and not with lifestyle choices. The supercentenarians have average rates of cancer, heart disease, and stroke, although they have escaped many age-related diseases, and their smoking, alcohol, exercise and diet appear no different than among ordinary people. Furthermore, as noted in the article, the parents, siblings and children of the centenarians have also lived well beyond average.

Previously: Unlocking the secrets to human longevity and California’s oldest person helping geneticists uncover key to aging

Genetics, History, Immunology, Research, Science, Stanford News

Knight in lab: In days of yore, postdoc armed with quaint research tools found immunology’s Holy Grail

Knight in lab: In days of yore, postdoc armed with quaint research tools found immunology's Holy Grail

charging knightA human has only about 25,000 genes. So, it’s tough to imagine just how our immune systems can manage to recognize potentially billions of differently shaped microbial or tumor-cell body parts. But that’s precisely what our immune systems have to do, and with exquisite precision, in order to stomp invading pathogens and wanna-be cancer cells and leave the rest of our bodies the heck alone.

How do they do it?

Stanford immunologist Mark Davis, PhD, tore the cover off of immunology in the early 1980s by solving that riddle. As I wrote in  “The Swashbuckler,” an article in the latest issue of Stanford Medicine, T cells are one of two closely related, closely coordinated workhorse-warrior cell types that deserve much of the credit for the vertebrate immune system’s knack of carefully picking bad guys of various stripes out of the lineup and attacking them:

[Q]uite similar in many respects, B cells and T cells are more like fraternal than identical twins. B cells are specialized to find strange cells and strange substances circulating in the blood and lymph. T cells are geared toward inspecting our own cells for signs of harboring a virus or becoming cancerous. So it’s not surprising that the two cell types differ fundamentally in the ways they recognize their respective targets. B cells’ antibodies recognize the three-dimensional surfaces of molecules. T cells recognize one-dimensional sequences of protein snippets, called peptides, on cell surfaces. All proteins in use in a cell eventually get broken down into peptides, which are transported to the cell surface and displayed in molecular jewel cases that evolution has optimized for efficient inspection by patrolling T cells. Somehow, our inventory of B cells generates antibodies capable of recognizing and binding to a seemingly infinite number of differently shaped biological objects. Likewise, our bodies’ T-cell populations can recognize and respond to a vast range of different peptide sequences.

In the late 1970s, scientists (including then-graduate student Davis, who is now director of Stanford’s Institute for Immunity, Transplantation and Infection) unraveled the genetic quirks behind B cells’ ability to recognize a mind-blowingly diverse  set of different pathogens’ and tumor-cells’ characteristic molecular shapes. As a follow-on, Davis and a handful of colleagues – working with what would today be considered the most primitive of molecular-biology tools – isolated the gene underlying the T-cell receptor: an idiosyncratic and very important surface protein that is overwhelmingly responsible for T cells’ recognition of myriad pathogen- and cancer-cell-specific peptide sequences. And they figured out how it works.

The result? (Again from my article:)

With the T-cell receptor gene in hand, scientists can now routinely sort, scrutinize, categorize and utilize T cells to learn about the immune system and work toward improving human health. Without it, they’d be in the position of a person trying to recognize words by the shapes of their constituent letters instead of by phonetics.

Previously: Stanford Medicine magazine traverses the immune systemBest thing since sliced bread? A (potential) new diagnostic for celiac disease, Deja vu: Adults’ immune systems “remember” microscopic monsters they’ve never seen before, Immunology escapes from the mousetrap, Immunology meets infotech and Mice to men: Immunological research vaults into the 21st century
Photo by davidmclaughlin

Biomed Bites, Cancer, Dermatology, Genetics, Research, Videos

Spotting broken DNA – in the DNA fix-it shop

Spotting broken DNA - in the DNA fix-it shop

It’s Thursday. And here’s this week’s Biomed Bites, a weekly feature that highlights some of Stanford’s most innovative research and introduces Scope readers to innovators in a variety of disciplines.

Neon green streaks across the screen. The phrases “End mismatched ligation” and “Repair of DNA double-strand breaks” flash at me. Did I stumble across an online, genetic fix-it shop? Sort of -  in that Stanford biochemist Gilbert Chu, MD, PhD, studies broken DNA and has a website to match.

Chu describes his research in the video above: “We started out in the lab trying to understand and recognize DNA that’s been damaged by ultraviolet radiation, which causes skin cancer. This led to the discovery of a protein that turned out to be missing in patients with a very rare disease called xeroderma pigmentosum.”

XP afflicts about 1 in 1,000,000 people in the United States. Without the protein Chu mentioned, mutations and damage accumulates in sufferers DNA, causes cancers and extreme sensitivity to the sun.

Chu’s team has also developed methods that allow other researchers to examine the expression of genes across an entire genome and to determine which cancer patients might be harmed by treatment with ionizing radiation.

“The reason I got interested in this research is that as a member of the Department of Medicine, I am an oncologist and I’m very interested in trying to help cancer patients,” Chu said.

Learn more about Stanford Medicine’s Biomedical Innovation Initiative and about other faculty leaders who are driving forward biomedical innovation here.

Previously: Skin cancer linked to UV-caused mutation in new oncogene, say Stanford researchers, Radiation therapy may attact circulating cancer cells, according to new Stanford study and How ultraviolet radiation changes the protective functions of human skin

Genetics, Pediatrics, Research, Science, Stanford News

Move over CRISPR, there’s a new editor in town: Stanford-devised approach cures hemphilia in mice

Move over CRISPR, there's a new editor in town: Stanford-devised approach cures hemphilia in mice

A lot of attention has been paid lately to the idea of genome editing. This technique allows researchers to precisely modify an animal’s DNA to replace one version of a gene with another, or to add a working copy for a mutated gene. An approach called CRISPR/Cas9 in particular has garnered interest with its ease of use, ability to modify multiple genes, and relatively quick turnaround time when making specific strains of laboratory animals like mice for study.

Now pediatrician and geneticist Mark Kay, MD, PhD, has published  in Nature a new way to conduct genome editing that could give CRISPR a run for its money because it could be both safer and longer-lasting than other methods. As described in our press release:

The approach differs from that of other hailed techniques because it doesn’t require the co-delivery of an enzyme called an endonuclease to clip the recipient’s DNA at specific locations. It also doesn’t rely on the co-insertion of genetic “on” switches called promoters to activate the new gene’s expression.

Inclusion of endonucleases and promoters run the risk of a gamut of adverse effects in the recipient, from cancers if the promoter turns on the wrong gene in the genome to an unwanted immune response geared toward the foreign proteins. The researchers in Kay’s lab, including postdoctoral scholar and study lead author Adi Barzel, PhD, found a way around their use, and showed that it worked to enable mice with hemophilia to produce a missing blood clotting factor:

The technique devised by the researchers uses neither nucleases to cut the DNA nor a promoter to drive expression of the clotting factor gene. Instead, the researchers hitch the expression of the new gene to that of a highly expressed gene in the liver called albumin. The albumin gene makes the albumin protein, which is the most abundant protein in blood. It helps to regulate blood volume and to allow molecules that don’t easily dissolve in water to be transported in the blood.

The researchers used a modified version of a virus commonly used in gene therapy called adeno-associated virus, or AAV. In the modified version, called a viral vector, all viral genes are removed and only the therapeutic genes remain. They also relied on a biological phenomenon known as homologous recombination to insert the clotting factor gene near the albumin gene. By using a special DNA linker between the genes, the researchers were able to ensure that the clotting factor protein was made hand-in-hand with the highly expressed albumin protein.

As Kay, who is also a member of the Stanford Cancer Institute, the Stanford Child Health Research Institute and Stanford Bio X, explained, the integration of the clotting factor gene is key to the successful treatment (other clinical trials involving gene therapy for hemophilia rely on the expression of a free floating, unintegrated gene in the nucleus):

The real issue with AAV is that it’s unclear how long gene expression will last when the gene is not integrated into the genome. Infants and children, who would benefit most from treatment, are still growing, and an unintegrated gene could lose its effectiveness because it’s not copied from cell to cell. Furthermore, it’s not possible to re-administer the treatment because patients develop an immune response to AAV. But with integration we could get lifelong expression without fear of cancers or other DNA damage.

Previously: Gene “editing” could correct a host of genetic disorders, Policing the editor: Stanford scientists devise way to monitor CRISPR effectiveness and Both a doctor and a patient: Stanford physician talks about his hemophilia

Cancer, Events, Genetics, Imaging, Stanford News, Surgery, Women's Health

Don’t hide from breast cancer – facing it early is key

Don't hide from breast cancer - facing it early is key

cat_hiding-pgMy cat suffers from acute anxiety. Although she and I have lived together for more than 12 years, and the worst thing I’ve ever done to her was cut her nails, she’s terrified of me. (She’s also very smart – she runs from the sound of my car, but not my husband’s). During trips to vet, Bibs hides her eyes in the crook of my elbow.

It’s a strategy that’s only minimally effective. After all, what I can’t see, or don’t recognize, can still hurt me.

Take breast cancer. It terrifies most women. And if you don’t look for it, you won’t find it. But if you do look, and find it early, you might save your life and your breast, says Amanda Wheeler, MD, a Stanford breast surgeon. She joined other Stanford breast cancer experts at a recent public program sponsored by the Stanford Women’s Cancer Center called “The Latest Advancements in Screening and Treatment for Breast Cancer.”

“One of our biggest challenge is women are scared of breast cancer, but[we have to get] the word out that we have such great advances, we’ve just got to catch it early,” Wheeler said.

She pointed to a tiny dot on a screen. At that size, Wheeler said, breast cancer is almost 100 percent curable. She performs a small lumpectomy. If it’s a little bigger, she can still probably save the nipple.

And if the entire breast must be removed, surgeons like Rahim Nazerali, MD, come in. Nazarali explained the importance of choosing a reconstruction surgeon carefully: The doctor should be accredited by the American Society of Plastic Surgeons and have experience with microsurgery, preferably on the breast. There are different ways to remold a breast and doctors can use either a synthetic implant or a patient’s own tissue, from their abdomen, hips or thighs, Nazerali explained.

All of Wheeler and Nazerali’s artistry depends on expert imaging performed by specialists like Jafi Lipson, MD, whose message at the event was simple and encouraging.

Thanks to many new developments, mammography isn’t the only way to detect nascent breast cancers, Lipson said. Her team can employ 3-D mammography, or tomosynthesis, to reveal a layered look at a breast. And genetic screening, particularly for those with a history of breast cancer in the family, can provide the earliest warning signal of all, the breast cancer team said.

Women no longer need to hide their eyes from the risk, the experts emphasized. Women should take a peek – there’s help coping with what they may find.

Previously: Screening could slash number of breast cancer cases, The squeeze: Compression during mammography important for accurate breast cancer detection, Despite genetic advances, detection still key in breast cancer, NIH Director highlights Stanford research on breast cancer surgery choices, Breast cancer awareness: Beneath the pink packaging and Using 3-D technology to screen for breast cancer
Photo by Notigatos

Cancer, Genetics, Medicine and Society, Research, Stanford News, Women's Health

Screening could slash number of breast cancer cases

Screening could slash number of breast cancer cases

dna-163466_1280Should every newborn baby girl be genetically screened to prevent breast cancer? Obviously, that isn’t cost-effective — yet. But if it were, would it be worthwhile?

A previous study said no. But research published today in Cancer Epidemiology, Biomarkers & Prevention by Stanford researchers suggests otherwise.

Led by senior author Alice Whittemore, PhD, the team examined 86 gene variants known to increase the chances of breast cancer. They created a model that accounted for the prevalence of each variant and the associated risk of breast cancer. Each possible genome was then ranked by the likelihood of developing breast cancer within a woman’s lifetime.

“It was quite a computational feat,” Whittemore told me.

Working with Weiva Sieh, MD, PhD; Joseph Rothstein, PhD; and Valerie McGuire, PhD, the team found that the riskiest top 25 percent of gene combinations predicted 50 percent of all future breast cancers.. Those women would then have the opportunity to get regular mammograms, watch their diets and make childbearing and breast-feeding decisions with the awareness of their higher risk. Some women might even select, as Angelina Jolie did quite publicly, to have their breasts removed.

“The main takeaway message is we can be more optimistic than previously predicted about the value of genomic sequencing,” Whittemore said. “But we still have a way to go in preventing the disease.”

“Our ability to predict the probability of disease based on genetics is the starting point,” Sieh said. “If a girl knew, from birth, what her inborn risk was, she could then make more informed choices to alter her future risk by altering her lifestyle factors. We also need better screening methods and preventative interventions with fewer side effects.”

“We want to focus on those at the highest risk,” Whittemore said.

Previously: Despite genetic advances, detection still key in breast cancer, NIH Director highlights Stanford research on breast cancer surgery choices  and Breast cancer awareness: Beneath the pink packaging 
Photo by PublicDomainPictures

Biomed Bites, Genetics, Research, Stanford News, Videos

DNA architecture fascinates Stanford researcher – and dictates biological outcomes

DNA architecture fascinates Stanford researcher - and dictates biological outcomes

It’s time for the next edition of Biomed Bites, a weekly feature that highlights some of Stanford’s most innovative research and introduces Scope readers to groundbreaking researchers in a variety of disciplines. 

It’s a puzzle that would delight puzzle master Will Shortz: How do you pack 2 meters of DNA into a container (the nucleus) only .000005 meters wide? Precisely, and according to plan, it seems. Stanford biophysicist Will Greenleaf, PhD, studies the architecture of the genome, building on the knowledge that DNA’s shape effects how a gene is expressed.

In the video above, Greenleaf, now an assistant professor of genetics, explains: “The genes have to be unpacked to be expressed. The mechanics of that are really fascinating.”

Greenleaf is a physics guy, earning a PhD in applied physics at Stanford to build on his undergraduate Harvard physics degree. He has also studied computer science and chemistry, bringing all of this knowledge to bear on demystifying the structure of DNA, and its RNA offshoots. Greenleaf and his team also develop new instruments needed to measure, see and manipulate DNA structure.

This is important for many reasons, but most directly to treat chromatinopathies, or diseases caused by the improper folding or structure of DNA and its associated proteins.

Learn more about Stanford Medicine’s Biomedical Innovation Initiative and about other faculty leaders who are driving forward biomedical innovation here.

Previously: Caught in the act! Fast, cheap, high-resolution, easy way to tell which genes a cell is using, “Housekeeping” protein complex mutated in about 1/5 of all human cancers, say Stanford researchers and Mob science: Video game, EteRNA, lets amateurs advance RNA research

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