Breakthroughs XIV

SCIENCE NEWS FROM P&G BEAUTY VOL. XIV 2007  

DANDRUFF MYSTERIES REVEALED WITH GENOME SEQUENCING

In a breakthrough genomic discovery recently published in Proceedings of the National Academy of Sciences (PNAS), scientists from P&G Beauty successfully sequenced the entire genome of the fungus Malassezia globosa (M. globosa), which is responsible for the onset of dandruff and other conditions in humans. This work establishes P&G Beauty as the leader in scalp health research and innovation in dandruff treatment.

Implications

The health implications of this research are significant, as dandruff, and the more severe seborrheic dermatitis, affect more than 50 percent of the human population. Furthermore, the family of Malassezia species affects a wide range of human health issues, including individuals with early and compromised immune systems, such as infants and those suffering from autoimmune diseases. This fungus family also plays a role in skin and respiratory allergies.

"What started as an effort to unlock the mechanism behind dandruff has opened the scientific doors for the development and enhancement of treatments for dandruff and many more Malassezia-related conditions," said James Schwartz, PhD and Research Fellow at P&G Beauty.

Malassezia is a culprit in conditions mild to severe, but almost nothing was understood at the molecular level before this research. The genetic sequencing of M. globosa has expanded the range of potentialtreatment targets from a few observational characteristics to now more than 4,000 molecular targets.

Image of M. globosa

Dandruff Defined

M. globosa, which is among the smallest of the sequenced free-living fungal organisms, is comprised of 4,285 genes -roughly 300 times fewer base pairs than are found in the human genome. A common fungus that lives on the skin of humans, M. globosa feeds off of fatty external lipids. Humans naturally secrete sebum and other lipids onto the scalp, creating a prime environment for M. globosa to thrive. The human scalp can host up to 10 million M. globosa. Symptoms of dandruff and seborrheic dermatitis occur when three factors come together: genetic susceptibility for an inflammatory response, the presence of sebum on the scalp and the presence of M. globosa.

Sequencing Story

Due to the earlier use of less-accurate culture-based technologies, scientists incorrectly assumed for years that dandruff was caused by a different type of fungus (Malassezia furfur). With the use of molecular science and bioinformatics, the team uncovered the correct fungal species, eventually leading to the complete sequencing through a unique step-by-step process.

Beyond Dandruff

In addition to genome implications for humans, this information will be important to researchers studying agricultural science. M. globosa is closely related to multiple common plant pathogenic fungi that cause disease on corn, wheat and other important food source crops. Comparative genomic studies are now underway that could lead to new strategies for managing these related crop diseases.

Corn smut (Ustilago maydis) fungi

"A complete genomic sequencing of a Malassezia genome opens tremendous opportunities for researchers," said Thomas Dawson, PhD, a Principal Scientist at P&G Beauty and the principal author of the PNAS study. "It's amazing that the understanding of the genetic make-up of a microscopic organism can have broad implications ranging from human health to agricultural science."

UNDERLYING CAUSES OF SkIN AGING FOUND

Gene Expression Research Reveals Causes of Wrinkles, Age Spots

In the past, scientists studying aging skin have looked at various skin properties - thickness, color, moisture barrier, proteins, and internal cell structures. Today, P&G Beauty scientists are studying the differences between young and aged skin at the most fundamental level possible - gene expression. "The expression of your genetic code as it reacts to environmental change controls all the metabolic processes necessary for good skin health and function," says P&G Beauty Geneticist Dr. Jay Tiesman, PhD. "Now we understand which genes become either disabled or overactive as your skin gets older, resulting in the physiological changes we see as wrinkles and age spots."

Young vs. Old, Protected vs. Exposed

Research analyzed skin samples collected from ten young and ten aged female subjects (18-20 and 60-67 years). Scientists collected skin biopsies of buttocks to test intrinsically aged skin and biopsies of forearms for extrinsically aged skin. The buttock and forearm biopsies were selected because of their relative exposure, or lack thereof, to environmental elements that may impact aging. Additionally, Affymetrix gene chip technology was used to examine the gene expression differences in the samples to reveal the underlying biological mechanisms responsible for the appearance of skin aging. The study allowed scientists to identify pathways that are active in young skin but inactive in old skin, as well as those that are overly active in older skin.

Young and old skin biopsies

Sun Exposure Alters Skin Immune Function

One provocative finding was that aging associated with environmental factors, such as Uv, not only accelerated the changes in natural aging genes as expected, but also turned on other gene responses. For example, the study demonstrates the magnitude of altered immune and inflammatory gene expression resulting from the photodamage process. This is important as recent scientific literature shows that UV-altered immune response in skin can increase susceptibility to skin cancer.

Driving Future Skin Anti-Aging Advances

This research is expected to drive breakthrough advances in both prevention and treatment of the signs of aging skin over the coming decades. By understanding how the expression of specific genes are modulated by the aging process, scientists now have the means to develop treatments to modify those processes that age skin considerably. "In the future, certain processes such as inflammation, proteolysis, lipid biosynthesis, or cellular differentiation, known to be involved in the breakdown of skin as it ages, may be able to be regulated," speculates Dr. Michael Robinson, Principal Scientist, P&G Global Biotechnology, lead author on the study.

Myths & Facts

• The rate at which you get wrinkles is completely dependent on your genetics. MYTH - Many scientific studies of identical twins show that environmental factors such as smoking and UV exposure can accelerate the onset of wrinkles. Good skin care and sun protection habits will help keep you looking more youthful longer, no matter what your genetic inventory.

• Pollution can contribute to the appearance of aging at the skin's surface. FACT - Aging skin loses its ability to produce nicotinamide adenine dinucleotide (NADH) and nicotinamide adenine dinucleotide phosphate (NADPH) - which are the energy reservoirs for cells. This loss reduces the skin's ability to repair itself from damage caused by free radicals, which are often generated by environmental stressors, like UV exposure and pollution. The result is wrinkles, loss of texture, impaired barrier function, dryness, sagging and age spots.

STRANGELY BEAUTIFUL

Fiber damage is a significant concern for the millions of men and women who color their hair. Regular color treatment breaks down the F-layer, changing the hair's surface energy causing hair to become hydrophilic (water-loving) instead of hydrophobic (water-repellant). Hydrophilic hair is more easily damaged and less smooth and shiny.

To guide development of hair colorants to reduce hair fiber damage, P&G Beauty researchers developed a new method for efficiently evaluating the surface energy changes of hair fibers. In this "dual fiber wetting" test, a drop of water is set on two hair strands. Then the speed of wetting and contact angles are measured indicating relative surface energy and hydrophobicity.

The images to below illustrate changes between non-color treated and color treated hair: on the right, bleach damaged hair fibers have become hydrophilic as seen in the flattened-out shape and acute contact angle. on the left, undamaged hair fibers repel the water so that it stays in a tight sphere with an obtuse contact angle.

Undamaged hydrophobic hair (left) and bleach damaged hydrophilic hair (right)

LAB NOTES

Body Wash Benefits for Atopic Dermatitis

Atopic dermatitis (AD) is a chronic skin condition characterized by skin inflammation and pruritis (itch) also known as eczema. New research jointly conducted by independent dermatologist Zoe Draelos, MD, and P&G Beauty researcher, keith Ertel, PhD, shows that a dual phase moisturizing body wash can shorten the length of an AD breakout, when used as an adjunct to steroid cream therapy.

In a four-week double blind clinical study, 60 females ages 18-65 with mild to moderate active AD were assigned either a dual phase petrolatum depositing body wash or dermatologist recommended "mild" syndet bar soap for daily showering. All subjects received 0.1% triamcinolone acetonide (steroid cream) to apply twice daily to their AD lesions, in addition to their assigned treatments.

AD disease resolution at two and four weeks

Scientists evaluated patients' progress while using the steroid cream against the standard expectation of improvement at two weeks and clearing at four weeks. It also judged how well each subject tolerated the assigned cleanser at the four week evaluation.

After two weeks, 79.3% of subjects assigned to use dual phase body wash showed improvement, compared to 26.7% of subjects assigned to use the syndet bar. After four weeks, 92.9% of subjects assigned to use dual phase body wash showed clearing, compared to 24.1% of subjects assigned to use syndet bar.

FAST FORWARD

In vitro human cornea and skin equivalents allow P&G Beauty scientists to identify the body's responses to common product ingredients. While structurally these equivalents provide a realistic example of the eyes and skin, historically they have not been able to reveal pain or sensitivity to the ingredients.

P&G Beauty scientists in collaboration with the University of Ottawa Eye Institute have shown that adding nerve cells to the tissue-engineered corneas results in a stronger equivalent that responds to pain. These researchers also recently mirrored the technology in skin equivalents to improve opportunities for both skin safety and efficacy testing. They found that adding nerve cells to tissue cultures actually results in a more realistic stratification of the epithelium, in addition to improving capacity of the cultures to respond to topical irritants.

Model of the inclusion of nerve cells

Since these pain-responsive cornea and skin equivalents are a more realistic in vitro model of human tissue, they will provide more realistic responses for in vitro safety and efficacy testing of new chemicals in the future. Beyond in vitro testing, these models are also providing valuable clues to help scientists understand how best to design engineered tissues for transplantation research.

IN THE SPOTLIGHT

Tom Dawson, PhD

Scalp and hair follicle expert, Dr. Thomas Dawson, Jr., is an accomplished Principal Scientist in the P&G Global Biotechnology department.

Most recently, Dr. Dawson played an integral role in the sequencing of the Malassezia globosa (M. globosa) genome, a fungus that is responsible for the onset of dandruff and other skin conditions. Dr. Dawson recently presented this breakthrough research at the 21st World Congress of Dermatology in Buenos Aires, Argentina.

Additionally, Dr. Dawson has conducted multiple clinical trials on various scalp and hair follicle matter, and has published more than 30 original articles, chapters and papers, which have appeared in leading industry journals, including Journal of Cosmetic Science and the Journal of Investigative Dermatology.

Prior to joining P&G, Dr. Dawson was a Clinical Medical Genetics Fellow at the Duke University Medical Center, where he studied human metabolic disease, the identification of novel disease-causing genes, and collaborated in the identification and development of a novel drug to treat Type 2 glycogen storage disease.

  

Special Report: 21st World Congress of dermAtology

P&G Beauty was a Gold Patron sponsor of the 21st World Congress of Dermatology held in Buenos Aires, Argentina, September 30-October 5, 2007. Every five years, dermatologists, medical professionals and industry leaders from across the globe gather at the World Congress of Dermatology to learn about the latest scientific, treatment and product advancements in the dermatological field.

About the 21st World Congress

Hosted by the International League of Dermatological Societies, the 21st Congress emphasized issues relating to "Global Dermatology for a Globalized World." Specifically, of the 3,800 total studies presented, over 60 posters and presentations focused on dermatological issues facing various ethnic populations. Genomic research and technologies, especially as they relate to anti-aging, were also leading topics.

This year's meeting was attended by 13,411 industry leaders from 143 companies representing 117 countries. Furthermore, it was led by a scientific committee of premier authorities in the field, including Congress President, Ricardo T. Galimberti, MD, Director of the Department of Dermatology at the Buenos Aires Italian Hospital in Argentina; Secretary General Adrian M. Pierini, MD, Director of the Pediatric Dermatology Service at the Hospital de Pediatria in Buenos Aires; and Scientific Chairman Fernando Stengel, MD, Chief of the Division of Dermatology at the Clinicas Hospital in Buenos Aires.

 

 

P&G Beauty at the World Congress of Dermatology

 

p&g beAuty's presenCe At the World Congress

As a Gold Patron sponsor, P&G Beauty scientists hosted 21 talks and presented 10 cutting-edge scientific posters. They also led dynamic conversations and lectures at three P&G Beauty sponsored symposia:

• "Latest Advancements in Skin Health and Anti-Aging" This session provided an overview of skin care needs in varying global populations and addressed the role of inflammation and botanicals in managing skin disorders.
• "Cosmeceuticals: Practical Solutions for Common Problems" Scientists discussed the latest ingredients and treatment strategies evolving from recent biomolecular research.
• "Hot Topics in Hair and Scalp Science" This symposium examined the challenges involved in treating common hair and scalp disorders, including delivery, ingredients and patient compliance.

Additionally, over 6,000 people from 87 countries visited the P&G Beauty booth to learn more about the science behind Head and Shoulders® and Olay® products.

These activities and more were chronicled by world-renowned skin and hair expert, John Gray, MD, on P&G Beauty's World Congress of Dermatology blog, Day-to-Day with Dr. Gray. Dr. Gray's blog and P&G scientific content from the World Congress are available on the on the 21st World Congress of Dermatology Web pages.

sCientifiC innovAtion from p&g beAuty

The 21st World Congress theme, "Global Dermatology for a Globalized World," focused on dermatologic science that affects people worldwide. However, over the course of the meeting, two key topics emerged: genomic research and ethnic diversity research.

Genomic Research

More than 100 posters and talks involving genomics and gene expression emphasizing the importance of genomic science in today's medical research were presented at the meeting. The P&G Beauty genomics work was some of the most exciting, as evidenced by the award recognition it received.

Immune and Inflammatory Gene Expression Profiles of Chronological (Intrinsic) Skin Aging and PhotoAging

Michael Robinson, PhD, Principal Scientist at P&G Beauty, presented a poster on the ability to identify the exact processes and metabolic pathways that differentiate young versus old skin. Using skin biopsies collected from ten young female (18-20 years) and ten aged female (60-67 years) subjects, the study allowed scientists to identify pathways that are active in young skin but inactive in old skin, as well as those that are overly active in older skin, such as inflammation. His use of sophisticated genomics tools to better understand the genomic and biological mechanisms responsible for the appearance of skin aging was honored by the World Congress with "Outstanding Recognition."

 

Malassezia globosa and Restricta: Breakthrough Understanding of the Etiology and Treatment of Dandruff and Seborrheic Dermatitis through Whole Genome Analysis

Thomas L. Dawson, Jr., PhD, presented for the first time anywhere in the world his research that successfully sequenced the complete genome for Malassezia globosa (M. globosa), a naturally occurring fungus responsible for the onset of dandruff and other skin conditions. This discovery offers a host of new opportunities for the research community to improve on current treatments and study new therapies to fight M. globosa related conditions.

Detail of seborrheic dermatitis scale

Ethnic Diversity Research

More than 60 presentations and posters were given addressing skin and hair disorders among different ethnic populations that reiterated the World Congress theme and addressed the diversity of global dermatology. P&G Beauty collaborators and scientists shared new findings about skin and hair needs across different ethnicities:

Hair Breakage in Normal and Weathered Hair: Focus on the Black Patient

Amy J. McMichael, MD, presented research regarding the impact of hair care practices on the development of hair fragility and breakage. She discussed the prevalence of common disorders in various ethnic populations, the management of common hair and scalp disorders in select populations and new study findings on hair breakage among populations of African descent.

P&G Beauty sponsored hair care symposium

Similarities and Differences in Skin Care Needs and Disorders Across Various Global Populations

Alexa Kimball, MD, MPH, discussed skin health and differences among various global populations. She examined skin disorders resulting from medical and biological factors and habits, as well as the art of diagnosing common skin disorders. She also shared new results from a collaboration with P&G Beauty on the impact of ethnicity on prevalence of rosacea globally.

P&G BEAUTY SCIENCE

P&G Beauty Science has more than 1,800 scientists and technical employees working at 11 global technical centers with an unparalleled commitment to technology development. Company scientific efforts have resulted in over 3,500 active beauty care patents. This allows P&G to develop products uniquely suited for different types of hair and skin, and tailored to different cultures and climates.

P&G Beauty products help make beauty dreams real and grooming enjoyable every day for millions of women and men worldwide. With more than 100 brands available in nearly 130 countries, P&G Beauty delivered sales of more than $22 billion in fiscal year 2006/07, making it a leading global beauty company. P&G Beauty brands include: Pantene^®, Olay^®, Head & Shoulders^®, Max Factor^®, Cover Girl^®, Rejoice^®, Herbal Essences^®, Koleston^®, Clairol^®, Gillette^®, Sk-II^®, Wella^®, Joy^®  by Jean Patou, Hugo Boss^® and Lacoste^®. (NYSE: PG)

CONTACT INFORMATION

To talk to a P&G scientist or to learn more about ongoing research at P&G Beauty, contact:

Heather Cunningham P&G Beauty Science 513-626-2606