Ken Dill, PhD, professor and associate dean of research in the UCSF School of Pharmacy and international expert on theoretical approaches to determining how protein molecules fold, has been elected to the National Academy of Sciences (NAS). With this announcement, made by the Academy on Tuesday, April 29, 2008, Dill becomes the second NAS member of the School. "This election speaks to Ken's brilliance as a scientist," remarked Mary Anne Koda-Kimble, PharmD, dean of the School.

Not only is his work superior, his advocacy for science funding is tireless, she added. "Ken believes that the wellsprings for advances in drug discovery and development are to be found in the deepest reaches of academic basic science research. He fights for increased federal science funding for others because he believes in the promise of unfettered discovery."

Dill joins School of Pharmacy faculty member Jim Wells, PhD as a member of the NAS. With Dill's election, UCSF now counts 32 current members of the Academy.

Image Credit: Majedphoto.com

Full Story

UCSF's Ken Dill Elected to National Academy of Sciences

For the 29th consecutive year, the UCSF School of Pharmacy ranks first among US pharmacy schools in contract and grant funding from the National Institutes of Health (NIH), according to figures for fiscal year 2007. "The School's history of research funding success reflects its strength in both the most basic sciences that underlie drug discovery and increasingly the sciences required to translate these into patient care," says Mary Anne Koda-Kimble, PharmD, dean of the School.

"The latest ranking shows we have the track record required to meet our next big science goal," explains Koda-Kimble. "We are working to create a new framework for drug discovery and development that will result in faster, less expensive, more efficient methods to discover and develop new kinds of therapeutics -- including those that consider our genetic differences in drug response. It's an exciting time, a hopeful time. Continued funding from the NIH, other government sources, and increasingly private philanthropy is essential for our success."

Image Credit: Viral RNA Packing -- UCSF Computer Graphics Laboratory

Full Story

UCSF Among Top Universities in NIH Funding

More Information

UCSF School of Pharmacy Sets 5-year Plan in Motion

The UCSF School of Pharmacy continues to rank #1 among Doctor of Pharmacy (PharmD) degree programs in the United States according to results of a survey conducted in 2007 and published online on March 26, 2008 by U.S. News & World Report.

"Our success in rankings such as these has a lot to do with the fact that we don't rest on past achievements. We press ahead. Our goal is to educate pharmacists who will be innovative health care providers and advocates for the patients they serve. So in many ways, this ranking reflects the leadership of our graduates," said Mary Anne Koda-Kimble, PharmD, dean of the School.

As an example, she explains, the UCSF chapter of the American Pharmacists Association-Academy of Student Pharmacists (APhA-ASP) received the Chapter of the Year Award for achievement during the 2006-2007 academic year.

The UCSF School of Pharmacy is known worldwide for its leadership in pharmacy education. In the 1960s, the School was the first to train pharmacists as drug therapy specialists and not simply drug dispensers. This philosophical and academic shift positioned pharmacists as "clinical pharmacists" who, as active members of the health care team, began to work side by side with physicians and nurses to provide direct care to patients and consultation to patients' families.

In 1998, the School launched a 3-pathway PharmD curriculum that gives students, who are all clinically trained, the opportunity to further explore pharmaceutical care, pharmaceutical science, and pharmaceutical health policy and management in more detail. "In order for pharmacists to be leaders in the best, safe, effective use of medicines, pharmacy school curricula must be farsighted and continually refreshed," explained Koda-Kimble. UCSF School of Pharmacy graduates are now being recruited for not only clinical pharmacist positions but positions in pharmacy research, policy, and management.

The U.S. News and World Report survey of pharmacy schools was conducted in the fall 2007 for the 2008 rankings of PharmD programs accredited by the Accreditation Council for Pharmacy Education. Fifty-five percent of accredited programs surveyed responded. Survey subjects included deans, other administrators, and/or faculty in pharmacy programs. The report is available online and in hard copy and is entitled America's Best Graduate Schools, 2009 Edition.

More Information

• America's Best Graduate Schools, 2009 Edition, Pharmacy Ranked 2008, U.S. News & World Report
• UCSF School of Pharmacy PharmD Degree Program

Strategic Course 2007-2012

"It is a plan that looks at today's medications and the needs of patients and lays out an agenda to meet those needs," says Mary Anne Koda-Kimble, PharmD, dean of the UCSF School of Pharmacy. She refers to the School's 5-year strategic plan Pressing Ahead in New Directions, which presents 3 interlocking goals -- all focused on finding better ways to create drugs, use drugs, and improve health and save lives through drugs. The plan was released to the public on April 1, 2008.

While the plan is ambitious, the School is well positioned to meet its goals, Koda-Kimble explains. "As academics, we explore and discover, rather than develop and sell. Our work gives industry the information it needs to make smarter drugs that ultimately improve the health of our patients. It fuels the basic and drug-related discoveries of other scientists worldwide. It reveals better ways for health care providers and patients to use drugs safely and effectively. It shows how behavior, economics, policies, and procedures affect a patient's health," she says.

She emphasizes that the School does not target its work on one disease exclusively. Rather, it focuses on laying the foundations that ultimately relate to the prevention and treatment of many diseases. In these ways, she explains, the UCSF School of Pharmacy is a powerful force for improving today's medications and their use.

Koda-Kimble stresses that while today's drugs have been key to longer and healthier lives, they will pale by comparison to tomorrow's therapeutics. "Today's drugs are quite crude compared to what we know is possible in the future. They are created in standard ways. They treat the non-existent 'average' person. They end up in many places in the body, not just where they are needed to do their jobs. They are expensive to develop and expensive to use. The ways in which we deliver pharmacy care to patients also don't meet the needs of our patients, whose situations are always shifting based upon income, life situation, and health status," she says.

Koda-Kimble sees this situation change and the UCSF School of Pharmacy as a pivotal player in what she predicts will be a transformation in pharmaceutical science and pharmacy care. She poses a number of scenarios in the School's strategic plan, such as:

• What if we had a deeper understanding of the biological and chemical process that give rise to disease?
• What if we developed better ways to identify how and why medication errors and adverse events occur in hospitals and in the community?

The answers to these and other questions form the basis of the plan and its 3 goals, which were developed and endorsed by the School's faculty in consultation with the School's students, staff, alumni leaders, and external advisors, and with counsel from UCSF campus leaders.

Goal #1: Create a new framework for drug discovery and development

A major portion of the School's work will focus on creating a new framework for drug discovery and development through basic science research and research that takes fundamental discoveries and translates them into new therapeutics. To do this, School scientists will amplify their expertise in chemistry, mathematics, and physics -- through new faculty recruitments and new research programs -- to learn more about the biology of health and disease. They will create new tools, including those on the nanoscale, to poke and probe living systems, and in doing so understand how to better diagnose and treat disease. And they will expand their use of nontraditional approaches to predict which drugs will work best in, or even harm, individual patients or populations.

"The deepest problem today in discovering new medicines is that our concepts and approaches are too simplified and limited," says Ken Dill, PhD, associate dean for research at the UCSF School of Pharmacy. "In addition, we're finding that more and more disease mechanisms don't fit the standard single protein, single binding site paradigm in drug discovery. In other words, there is more to stopping some diseases than simply inserting a chemical key into a problem molecule and locking its function."

Dill and his research faculty colleagues in the School believe that key wellsprings for advances in drug discovery are to be found in the deepest reaches of basic research science. While the pharmaceutical and biotechnology industries spend their resources applying today's methods to discovering tomorrow's drugs, UCSF School of Pharmacy researchers focus on inventing tomorrow's methods of drug discovery.

"The drug industry has increasingly shifted its emphasis downstream from discovery toward product development, ceding ever more of the underlying basic research on new approaches and technologies to academic centers," says Dill. "This School is an academic center of accomplishment in the pharmaceutical sciences. We thrive on science challenges, and with the new plan we are continuing to flourish," he adds.

Goal #2: Ensure that more patients get the best results from their drugs

Against a backdrop of successful science and current innovation that will lead to more effective drugs with few or no side effects, UCSF School of Pharmacy faculty members are studying how to make sure more patients get the best results from the drugs they use. To the School's faculty, this means designing better clinical drug trials, new ways for pharmacists to care for patients, and new ways to decrease the medication errors that can jeopardize a patient's health and life. It also means empowering patients to better understand their own health conditions and medications and meeting the pharmacy needs of the world's underserved.

For Joseph Guglielmo, PharmD, chair of the School's department of clinical pharmacy, one line stands out in the School's strategic plan: "Take a pill and everything will be fine...if only it were that easy."

"'The relationship between any one drug and a patient is usually impersonal, sometimes volatile and inconsistent, and always complicated," explains Guglielmo.

Today's drugs do not consider the genetic differences in drug response among patients. Some cause mild to serious to life-threatening side effects. Drug effectiveness can be altered by such things as diet or exercise. And medications end up throughout the body, not just where they are needed to do their work.

"Pharmacists are the only health care providers trained to master the thousands of medications on the market. They are the drug experts. They all graduate as clinicians with Doctor of Pharmacy (PharmD) degrees, and in our School most go on to complete residency training," says Guglielmo. That kind of intellectual rigor is essential, he explains, especially for academic pharmacists, such as those in the UCSF School of Pharmacy, who teach pharmacy students, practice pharmacy themselves, and conduct the research from which changes in pharmacy care evolve worldwide.

"In addition to pharmacy clinicians, we're fortunate to have on our faculty exceptional health policy, health economics, and health care decision-making experts," says Guglielmo. The interface between the patient and the pill, he explains, has a lot to do not only with the patient's situation but with the situations in Washington, DC and in the public sector as well.

"In order to ensure that more patients get the best results from their drugs, we have to consider it all -- the patient, pill, medication care and delivery process, and the politics. Our research covers the full spectrum." One objective of the new plan is to develop a Medication Outcomes Research Center to study the effective and safe use of medications in the UCSF Medical Center and develop new models of excellence for the Medical Center and others, says Guglielmo.

Goal #3: Shape the future of pharmacy science, policy, education, and patient care by working in fresh and collaborative ways

"As we determined where we were headed through 2012, it became clear that we had to work in new ways to get there," says Koda-Kimble. "This, then, was the third goal of our plan. Our faculty members have traditionally worked across academic fields, and now we're combining fields in new ways. We're polishing a program to prepare more pharmacists to pursue research. Our students are teaching their peers -- students in medicine and nursing. Their leadership across the board is stunning. Our faculty and students are sharing their expertise with our global neighbors from Vietnam to Malawi and learning just as much or more about themselves and their work in exchange."

The School is also formalizing its commitment to diversity as part of its new strategic plan. The document describes diversity as that not only of people, but of perspectives, experiences, and academic and professional disciplines. "Science flourishes, healing is more likely to occur, and learning is enriched in a School community that is diverse in all ways," says Koda-Kimble. "We are especially committed to helping historically underrepresented minorities succeed."

Ongoing Mission

Koda-Kimble calls attention to the fact that while the School moves forward to accomplish the 3 goals outlined in its new strategic plan, it remains focused at all times on meeting its mission, which also includes:

• Educating PharmD students as leaders and experts in the safe and effective use of medicines.
• Educating PhD graduate students to be outstanding researchers across the spectrum from the basic to the health sciences.
• Providing strong postdoctoral training.

School and Campus Plans Align

While planning for Pressing Ahead in New Directions was under way, the UCSF campus began its first-ever strategic planning process, which included a redrafting of the campus mission statement. "As result, we in the School of Pharmacy slowed our planning timeline and participated in both campus and School planning. Our plan, Pressing Ahead in New Directions, and the campus plan, Advancing Health Worldwide, are in sync -- as they must be," explains Koda-Kimble.

Plan Affects Many

"Our plan was a long time in the making, concise in its final form, complementary to the campus plan, and we believe inspirational and hopeful to anyone who has ever used a medication -- and that is just about all of us," she says.

More Information

Marilyn Stebbins, PharmD, faculty member at the UCSF School of Pharmacy, was hired in 1996 by a 120-physician group practice to control the cost of prescribing. That work evolved into a model for cost effective medication therapy management (MTM) by pharmacists who work closely with physicians. Stebbins is now applying her expertise to help California's underserved seniors get the best medication value for their money. Stebbins and UCSF School of Pharmacy faculty colleagues formed the Partners in D program, which combines the expertise of faculty and student pharmacists from all seven of California's pharmacy schools to help low-income seniors get the best possible benefit from Medicare Part D, Medicare's Prescription Drug Coverage program. Learn more about Stebbins' work in Pharmacy Today.

Image Credit: Majedphoto.com

Full Story

Stebbins Integrates MTM Core Elements into Office-based Practice

More Information

Partners in D

UCSF School of Pharmacy faculty members and students were recognized with three honors at the 2008 annual meeting of the American Pharmacists Association (APhA) held March 14-17, 2008 in San Diego, California. Mary Anne Koda-Kimble, PharmD (image right), dean of the School recieved the 2008 Outstanding Dean Award. Faculty members Robert Day, PharmD (image center) and Glenn Yokoyama, PharmD (image left) were inducted as Fellows of APhA. The UCSF chapter of the APhA Academy of Student Pharmacists (APhA-ASP) received the Chapter of the Year Award, and former UCSF pharmacy student Lord Sarino, PharmD, and colleagues received the APhA Clinical Research Paper Award.

Image Credit: Majedphoto.com / Frank Farm

Koda-Kimble Receives Outstanding Dean Award

Mary Anne Koda-Kimble, PharmD, dean of the UCSF School of Pharmacy was honored by the American Pharmacists Association-Academy of Student Pharmacists (APhA-ASP) with the 2008 Outstanding Dean Award for significant support of APhA-ASP and her commitment to student welfare. At the awards ceremony, Koda-Kimble was described as a a servant leader, an advocate for professional development, and a dean who does not let any barrier impede a student's dream or idea. "Students with purpose and passion inspire me to clear the way for their work, and to find the time and resources that will help them reach their full potential, said Koda-Kimble at the awards ceremony. "I am very proud to receive this award...I am watching you (student pharmacists) closely and will try to follow your lead, for your success in enhancing health care for all is my purpose and my passion."

Koda-Kimble has served as pharmacy school dean at UCSF since 1998 after earning a PharmD degree from UCSF and subsequently joining the School's faculty as a practitioner, teacher, dean of students, then chair of the department of clinical pharmacy. She holds the Thomas J. Long Endowed Chair in Community Pharmacy Practice. In 2000 she became one of nine pharmacists elected to the Institute of Medicine for her major contributions to health and medicine. She has been a national leader in pharmacy throughout her career, as demonstrated by her presidency of the American Association of Colleges of Pharmacy. She is frequently invited to address national and international groups on topics ranging from over-the-counter medications to emerging issues in pharmacy and education. In addition , she has many publications, the best known of which is Applied Therapeutics, a text widely used by health professional students and practitioners throughout the world.

Day and Yokoyama Selected as APhA Fellows

Robert Day, PharmD, UCSF School of Pharmacy associate dean and Glenn Yokoyama, PharmD, department of clinical pharmacy faculty member, were inducted as Fellows of the American Pharmacists Association (APhA). Fellows have 10 years of professional experience and must have demonstrated progressive, exemplary professional service through APhA academies and other national, state, and local professional organizations.

Day has served as an advocate, advisor, and role model for all student pharmacists -- particularly those involved in the APhA Academy of Student Pharmacists (APhA-ASP) -- for more than 40 years. He has been an activist for patients and the rights of pharmacists to care for them. Throughout his career, he has consistently encouraged students to attend society meetings and to participate in debates as full-fledged professional partners. He has instilled in students a passion for creating professional change.

The hours Yokoyama devotes to professional service at the national and state levels reflect his dedication to pharmacy and its continued development. He is currently the treasurer of the APhA Foundation. He has served as president of the California Pharmacists Association (CPhA), the CPhA Foundation, the California Society of Health-System Pharmacists (CSHP), and the California State Board of Pharmacy. He is a CSHP fellow.

UCSF Chapter of APhA-ASP Receives Chapter of the Year Award

The UCSF chapter of the American Pharmacists Association-Academy of Student Pharmacists (APhA-ASP) received the Chapter of the Year Award for achievement during the 2006-2007 academic year. Co-presidents that year were Curt Allday and Luke Tso who organized chapter activities under the theme "Expect the Unexpected." "What a fantastic tribute to our students," said Mary Anne Koda Kimble, PharmD, dean of the UCSF School of Pharmacy. "This award recognizes their drive and commitment to the profession and their dedication to patient care. As important it signals that our students will be leaders upon graduation and agents of change. Congratulations!" The UCSF chapter won the award previously in 2000, the year the award was initiated.

2006-2007 UCSF APhA-ASP Co-presidents Luke Tso (left) and Curt Allday (right) hold Chapter of the Year Award as they celebrate with chapter members, Dean Koda-Kimble (center) and Associate Dean and Chapter Advisor Christopher Cullander (back row center) and Associate Dean Robert Day (back row right).

Image Credit: Kristin Harter

Sarino and Colleagues Receive Clinical Research Paper Award

A UCSF School of Pharmacy student research project that evolved into a research paper submission received the American Pharmacists Association (APhA) Clinical Research Paper Award. The paper, "Drug interaction between oral contraceptives and St. John's wort: Appropriateness of advice received from community pharmacists and health food store clerks," appeared in the January/February 2007 issue of the Journal of the American Pharmacists Association. The study identified a public health risk to women taking oral contraceptives, which might become ineffective if they also take St. John's wort. The lead author of the paper is former pharmacy student Lord Sarino, PharmD. Fellow former pharmacy students Kristy Dang, PharmD, Nahal Dianat, PharmD, Hera Djihanian, PharmD, and Neda Natanian, PharmD, are co-authors. Project advisors, who are also co-authors, were Peter Ambrose, PharmD, faculty member in the department of clinical pharmacy, and Karen Hudmon, DrPH, department of clinical pharmacy volunteer faculty member who is now with Purdue University.

James A. Wells, PhD, an internationally recognized biochemist and leader in the development of new technologies for engineering proteins and for identifying small molecules to aid drug discovery, has been named chair of the Department of Pharmaceutical Chemistry in the UCSF School of Pharmacy. His appointment is effective July 1, 2008. "Jim's appointment is terrific and timely," says Mary Anne Koda-Kimble, PharmD, dean of the UCSF School of Pharmacy. "Today's approach to drug discovery is cumbersome, complex, and produces few effective new drugs. We need new approaches and new technologies that arise from basic research, and industry is giving up more and more of this research to academic centers. Jim comes from industry and understands this well." Wells will succeed Thomas L. James, PhD, who has served as department chair since 1995.

Together with department faculty, Wells will help ensure the School's science goals are met. "We are well positioned to expand our science of drug discovery and synthetic biology in collaboration with our science colleagues on campus and beyond. We plan to understand more deeply the fundamental chemistry that underlies health and disease. And we'll create needed new research tools and technologies to find better ways to discover and develop drugs. This scientific vision was developed under the School's two science department chairs and supported by our whole School faculty," explains Wells. "I was involved in developing it and look forward to completing what we have challenged ourselves to do."

Image Credit: Majedphoto.com

Full Story

Wells to Chair UCSF Department of Pharmaceutical Chemistry

Sharon Youmans, PharmD, MPH, UCSF School of Pharmacy faculty member, has been named to the new position of Associate Dean of Diversity. The appointment was announced February 7, 2008 by School of Pharmacy Dean Mary Anne Koda-Kimble, PharmD.

Full Story

UCSF School of Pharmacy Names First Associate Dean of Diversity

Brian Shoichet, PhD, School of Pharmacy faculty member and Brian Feng, PhD, former staff research associate with the School, and colleagues have discovered that many amyloid inhibitors, which scientists had hoped would keep "sticky" amyloid protein fibers such as those associated with Alzheimer's disease from aggregating in brain tissue, actually clump together themselves. This would make these amyloid inhibitors useless as targeted therapies against amyloid in the brain. In addition, in their clumped form, they inhibit most other proteins with which they come in contact. Their work appears in the January 27, 2008 issue of Nature Chemical Biology under the title "Small-molecule aggregates inhibit amyloid polymerization."

"A cautionary conclusion to emerge from these studies," write the authors, "is that chemical aggregators may be common among inhibitors of amyloid fibrillization."

Full Story

Small molecule aggregates inhibit amyloid polymerization

B. Joseph Guglielmo, Jr., PharmD, School of Pharmacy chair of the department of clinical pharmacy, comments on the last line of defense to the methicillin-resistant Staphylococcus aureus (MRSA), a bacterium that has now spread from hospitals to schools, gyms, homes and beyond through human-to-human contact. Guglielmo is an expert in the drug treatment of infectious diseases and creator of the UCSF Medical Center's antimicrobial management program.

Image Credit: CDC/Janice Carr

Full Story

Bacteria Race Ahead of Drugs

More Information

Antimicrobial Drug Management Program Succeeds through Teamwork

School of Pharmacy faculty member and computational biologist Andrej Sali, PhD, and international colleagues, have developed new techniques to reveal the architecture of large protein complexes within cells. Their ultimate goal is to see how these complexes interact in real time - however fleeting the encounters. "The better we understand the architecture and interplay of protein communities inside our cells, the better we will understand our biology in health and disease," says Sali.

Their research appears twice in Nature, November 29, 2007 under the titles "Determining the architecture of macromolecular structures" and "The molecular architecture of the nuclear pore complex." The papers were rated by Nature editors as their favorite among 2007 cell biology papers. "Determining the architecture of macromolecular structures" was chosen as one of Chemistry and Chemical Engineering News 2007 chemistry highlights. It also appeared on December 26, 2007 as #1 among interesting papers published in the biological sciences by the Faculty of 1000 Biology. The second Nature paper appeared on the same day as the #2 rated paper by the same group.

"Andrej's work on protein architecture is one of those exciting, defining advances in science," says Kathy Giacomini, PhD, chair of the UCSF School of Pharmacy's department of biopharmaceutical sciences. "The ramifications for our understanding of biology are immense."

Image Credit: Majed

Sali and Colleagues Create Technique to Reveal the Architectures of Large Protein Assemblies

--Jeff Norris, UCSF Office of Public Affairs

In a tour de force, a UCSF faculty member and computational biologist - in collaboration with his colleagues at Rockefeller University - has invented a new approach to solve a long-standing protein puzzle.

Imagine a puzzle that teams of scientists around the world have been trying to solve for decades, and the excitement within the science community the day the picture finally becomes clear.

Exciting is what that day and subsequent days have been like for UCSF computational biologist Andrej Sali, PhD, faculty member in the UCSF School of Pharmacy. Sali’s research team collaborated with the research groups of Michael Rout, PhD, and Brian Chait, DPhil, at Rockefeller University to develop a combined experimental and computational approach for determining macromolecular architectures. They have set scientists buzzing by at last figuring out how 456 protein puzzle pieces that make up the nuclear pore complex (NPC) fit together to form a key structure within living cells.

It is one of the biggest, most complicated protein assembly structures that researchers have ever determined at this level of detail. To help solve the structure, Sali and UCSF postdoctoral fellow Frank Alber, PhD, developed integrated modeling platform (IMP) software, which has proved to be a powerful new bioinformatics tool.

In a scientific world where it is becoming easier for researchers to accumulate a wealth of data, scientists are increasingly challenged to make the best use of it all. IMP illustrates the value of developing new computational tools.

Solving this grand protein puzzle, unlike finishing a cardboard puzzle picture, is not an idle accomplishment. IMP eventually might have lifesaving consequences by providing a new source of structural clues to use in molecular drug design, for instance.

By tackling such a large and complex structure as the NPC, and by finishing a puzzle that other researchers could not, Sali and colleagues have demonstrated IMP’s potential. With IMP, a worldwide community of scientists has gained a powerful tool to tackle a broad range of molecular puzzles of their choice.

“To understand the workings of a living cell, we need to know the architecture of its molecular assemblies,” Sali says.

In the cells of organisms ranging from single-celled yeast to humans, the NPC is the major gateway that guides molecular traffic in and out of a cell’s nucleus. Many molecular agents and messengers that pass through this portal help control the activation of genes, in turn shaping the cell’s actions and responses.

The UCSF researchers and their collaborators describe IMP and its use in determining the NPC structure in yeast in two reports in the November 29, 2007, issue of Nature. Online, these two reports have for weeks ranked among the most viewed in the scientific literature.

Sali and collaborators envision that IMP, coupled with recent advances in electron microscopy and other experimental techniques, could serve as the foundation for the unprecedented study of many molecular interactions throughout the cell on a grand scale.

Just as a picture-puzzle solver uses different types of information – colors, sizes, and shapes, for example – IMP translates different types of laboratory and modeling data into a common language to describe rules and constraints that limit the possible spatial relationships among proteins and their parts.

“The most important aspect of our approach is its potential to use simultaneously almost any conceivable type of information to determine structures,” Sali says.

The experimental data input includes measures of possible error or uncertainty. IMP uses these measures to help score structural solutions that meet the constraints. Given enough good data, researchers can use IMP-generated rules to transform a randomly strewn batch of protein puzzle pieces into one or just a few possible solutions.

IMP is highly scalable. Researchers can use it to solve large structures of hundreds of proteins. Or, with greater definition, they can use it to determine the structures of much smaller protein couplings, Sali says.

One established technique for determining protein structure in atomic detail is X-ray crystallography. However, the technique requires crystals of purified proteins, and not all protein combinations form crystals, especially when the structure of interest consists of multiple, different proteins.

Another technique, nuclear magnetic resonance (NMR) spectroscopy, also provides high-definition structural data. But when using NMR, researchers must break proteins into small pieces for structural analysis.

At the other end of the size spectrum, large molecular assemblies comprising many proteins can be outlined accurately using electron microscopy. However, these outlines provide only limited information about how individual proteins are arranged within the structure.

IMP accommodates data from all these standard methods, as well as data from unconventional techniques for determining structure. For instance, to help solve the NPC structure, Rout and Chait developed new protocols for a technique called “affinity purification,” and used them to more precisely determine which proteins are in proximity to each other within the larger protein complex.

IMP also can incorporate modeling data from other computational programs.

“We are making IMP freely available in the hopes that it will be used very broadly as a framework for efforts by other scientists,” Sali says. “Others will be able to develop additional software modules to handle new kinds of data that will work with IMP.”

Related Story

Poring over Proteins: A Conversation with Biopharmaceutical Scientist Andrej Sali

More information

Nature, December 13, 2007
The molecular sociology of the cell
http://www.nature.com/nature/journal/v450/n7172/full/nature06523.html

Nature, November 29, 2007
Determining the architectures of macromolecular assemblies
http://www.nature.com/nature/journal/v450/n7170/full/nature06404.html

Nature, November 29, 2007
The molecular architecture of the nuclear pore complex
http://www.nature.com/nature/journal/v450/n7170/full/nature06405.html

Research Highlights, Nature editors “favourite” among 2007 cell biology papers
http://www.nature.com/nature/journal/v450/n7173/full/4501131b.html

Faculty of 1000 Biology (search on Andrej Sali)
http://www.f1000biology.com/browse/

2007 Chemistry Highlights, Chemical and Engineering News
http://pubs.acs.org/cen/coverstory/85/8552cover.html

Some leukemia cells supercharge cell pumps to get rid of chemotherapy. UCSF School of Pharmacy faculty member and pharmacogenetics researcher Deanna Kroetz, PhD, is aiming toward a simple way to identify these tumors, select the best treatment and avoid complications.

Full Story

Leukemia Survival and Pharmacogenetics

Health economist Leslie Wilson, PhD, faculty member in the UCSF School of Pharmacy, studies the ratio of cost to benefit, the benefit alone, or the cost alone of health treatments, educational interventions, and other activities that can ultimately impact a patient's health. One of her latest research projects focuses on Chagas' disease in the California blood supply and the cost of screening blood supplies for the disease compared to the health benefit. Learn more about Wilson's work in Science Café, a UCSF weekly column highlighting the culture, conduct, and community of science.

Full Story

A Bug in Our Blood: A Conversation with UCSF Health Economist Leslie Wilson

What began as a fascination with fish when he was a child eventually led Esteban Burchard, MD to study genetic differences behind asthma risk. Burchard, who is a physician scientist and faculty member in the UCSF School of Pharmacy, has uncovered differences in asthma risk and medication effectiveness in Latino subgroups that have profound implications for research, health care, and public policy. Learn more about Burchard's work in Science Café, a UCSF weekly column highlighting the culture, conduct, and community of science.

Full Story

Family Trees: A Conversation with Physician-Scientist Esteban Burchard

UCSF student pharmacists relate science to the everyday lives of 5th-graders at San Francisco's Rosa Parks Elementary School through a special program now in its second year. The Rosa Parks Science Discovery Program was developed by student pharmacist Ashish Patel and implemented by Patel and his peers, who are members of the Student National Pharmaceutical Association of UCSF. "Today we're learning about molecules and atoms from real scientists, and I can't wait to go home and tell my mom and dad about what I learned," said 10-year-old Diamond Mims.

Full Story

Project Teaches the 'Magic of Science' in Western Addition

More Information

Student National Pharmaceutical Association of the University of California, San Francisco

Leslie Z. Benet, PhD, faculty member in the UCSF School of Pharmacy delivered the Seventh Distinguished Clinical Research Lecture to the UCSF faculty on October 17, 2007 on UCSF's Parnassus campus. The lecture is UCSF's highest recognition for excellence in clinical research. Entitled, "Clearance Isn't Only a Big Sale and Transporters Aren't Limited to Trucks," Benet's remarks reflected both his well-known wit and his seminal contributions to the development of clinically relevant pharmacokinetic parameters such as clearance. The lecture is awarded by the San Francisco division of the Academic Senate.

Tom Ferrin, PhD, faculty member in the UCSF School of Pharmacy, is an expert in the use of computation and computer-generated images and simulations of biological molecules to understand how molecules act and interact. He uses this knowledge to better understand biology and to solve biological problems such as those involved in drug design. The challenge is daunting, says Ferrin, "If humans have an estimated 100,000 proteins, you see how large the number of possible combinations there are." Ferrin directs the UCSF Resource for Biocomputing, Visualization, and Informatics, which is known worldwide for its science and software. Learn more about Ferrin and his work in Science Café, a UCSF weekly column highlighting the culture, conduct, and community of science.

Full Story

Visualizing Life: A Conversation with Tom Ferrin, PhD

Mary Anne Koda-Kimble, PharmD, dean of the UCSF School of Pharmacy is the 2007 recipient of the Paul F. Parker Medal for Distinguished Service to the Profession of Pharmacy. The award was given October 14, 2007 by the American College of Clinical Pharmacy at its annual meeting in Denver, Colorado.

Full Story

Koda-Kimble to Receive 2007 Parker Award

Research by Nadav Ahituv, PhD, faculty member in the UCSF School of Pharmacy, shows that laboratory mice that had specific sequences of their DNA removed eat, grow, and reproduce normally. The stretches of DNA deleted by Ahituv are referred to as ultraconserved DNA that have been protected throughout evolution and are shared by humans. As in classic genetic research, Ahituv "took out" ultraconserved DNA sequences -- one by one -- to see what happened. He was surprised that, in fact, nothing happened. In retrospect, the results are more interesting, says Ahituv, who expected to see effects such as fertility problems. Why are these elements conserved over time? Ahituv is investigating. Learn more about Ahituv's research on Science Café, a UCSF weekly column highlighting the culture, conduct, and community of science:

Full Story

Mice or Men? How Important Is Conserved DNA? A Conversation with Geneticist Nadav Ahituv

A research paper authored by UCSF School of Pharmacy faculty member Brian Shoichet, PhD, and colleagues appeared in the September 2007 list of The Nature Top Ten. The listing includes articles most frequently downloaded from the Nature website the preceding month. The article was also featured as Nature's cover story in its August 16, 2007 print edition.

More Information

• Editor's Summary: Form Finds Function
• Structure-based activity prediction for an enzyme of unknown function
• Scientists Reveal Enzyme's Function by Its Structure