What will be the exciting new biological research areas in the next five years

March 26, 2009
HHMI Gives 50 Early Career Scientists a Jump on Their Next Big Idea

Fifty of the nation’s best early career science faculty will have more time and resources to focus on their boldest—and potentially transformative—research ideas with support from a new initiative from the Howard Hughes Medical Institute.

Each HHMI Early Career Scientist will receive a six-year appointment to the Institute and, along with it, the freedom to explore his or her best ideas without worrying about where to find the money to fund those experiments. HHMI’s investment of approximately $200 million will allow these researchers to concentrate on making discoveries in the laboratory and training the next generation of scientists.

HHMI will provide each Early Career Scientist with his or her full salary, benefits, and a research budget of $1.5 million over the six-year appointment. The Institute will also cover other expenses, including research space and the purchase of critical equipment.

The selected scientists, who are at 33 institutions across the United States, have led their own laboratories for two to six years. During that time, many have made considerable contributions to biomedical research. Energetic and passionate about a broad range of scientific questions, this group of scientists is at a career stage that many consider to be a scientist’s most productive—and most vulnerable.

In today’s constrained research funding environment, many early career faculty find it difficult to establish and develop their research programs. They often launch their own labs with start-up funds from their host institution. That support is provided with the expectation that the scientist will establish his or her own research program with independent funding.

The creativity and energy that researchers bring to starting their own labs can quickly be sapped by the time-consuming and often frustrating quest for funding. Within a few years of a new faculty appointment, a researcher's institutional start-up funds typically come to an end. Pressure to secure federal grant money may lead to “safe” grant proposals. As a result, creative and potentially transformative research projects may fall by the wayside.

In 2007, HHMI began to look for opportunities to diversify its research portfolio. As the Institute’s scientific leadership considered where HHMI’s resources could have the greatest impact, the answer was clear: The problems facing early career faculty had reached a point where the situation had become a threat to the vitality of the nation’s biomedical research capabilities. The Institute decided to establish a new research program to provide much-needed support to some of the nation's best early career faculty at a time when they most need the help.

“We saw a tremendous opportunity for HHMI to impact the research community by freeing promising scientists to pursue their best ideas during this early stage of their careers,” said HHMI President Thomas R. Cech. “At the same time, we hope that our investment in these 50 faculty will free the resources of other agencies to support the work of other outstanding early career scientists.”

“The selection of these early career scientists is the first HHMI competition that I have actively participated in,” said HHMI President-elect Robert Tjian, who will assume his new role on April 1. “Overall, I am very pleased the Institute has chosen to support the careers of these high-quality researchers.”

In March 2008, HHMI unveiled its new Early Career Scientist program and announced a nationwide competition seeking applications from the nation’s best early career scientists. Those working in all areas of basic biological and biomedical research and areas of chemistry, physics, computer science, and engineering that are directly related to biology or medicine were invited to apply. The competition drew more than 2,000 applicants. To maximize the impact of HHMI’s support, individuals who were selected in the competition cannot hold more than one early career award from another agency or foundation.

In selecting the finalists, HHMI was guided by the same “people, not projects” philosophy that defines its investigator program. Like HHMI investigators, the Early Career Scientists will have the freedom to explore and, if necessary, change direction in their research.

The 50 scientists selected in the competition will use this freedom to take on a broad range of scientific challenges. Among the projects underway in their laboratories are the identification of the genes and mechanisms that control regeneration in flatworms and zebrafish, the development of stem cell models for neurodegenerative disease, mapping of the neural circuits that process sensory information, and characterizing the forces that move cells to create new tissues and organs.

“These scientists are at the early stage of their careers, when they are full of energy and not afraid to try something new,” said Jack Dixon, HHMI vice president and chief scientific officer. “They have already demonstrated that they are not apt to play it safe—and we hope they will continue to do something really original.”

The newly selected scientists have let little stand in the way of their scientific curiosity. Many are taking interdisciplinary approaches and forging innovative collaborations to broaden the impact of their work. To tackle the scientific questions they consider most important, others have immersed themselves in fields in which they have never been formally trained—such as Columbia University’s Eric Greene, who taught himself the intricate techniques of single-molecule biophysics, which he now uses to study the behavior of individual DNA repair proteins.

When existing research tools have proved inadequate, some of these scientists have created their own. For example, more than 200 laboratories around the world are studying neural circuits in living animals with the aid of a technique Stanford University’s Karl Deisseroth created for turning on groups of neurons with a pulse of light. And in his quest to understand how tuberculosis bacteria keep themselves alive in their host, Christopher Sassetti at the University of Massachusetts Medical School invented a method of sifting through large quantities of genetic information to pinpoint genes that are essential for survival.

Similarly, when fruit flies, mice, and other traditional laboratory models have not suited their studies, these scientists have sought out model organisms that do: a spiny Canadian fish for insight into how species co-evolve with other organisms, lizards that reproduce asexually as a model for genetic diversity, and a shape-shifting bacteria for the study of cell-signaling circuitry.

The 41 men and 9 women will begin their six-year, nonrenewable appointments to HHMI in September 2009. The Institute anticipates a second Early Career Scientist competition in 2012.

The Howard Hughes Medical Institute

The Howard Hughes Medical Institute, a nonprofit medical research organization that ranks as one of the nation's largest philanthropies, plays a powerful role in advancing biomedical research and science education in the United States. In the past two decades HHMI has made investments of more than $8.3 billion for the support, training, and education of the nation's most creative and promising scientists.

HHMI's principal mission is conducting basic biomedical research, which it carries out in collaboration with more than 60 universities, medical centers, and other research institutions throughout the United States. Approximately 350 HHMI investigators, along with a scientific staff of more than 2,000, work at these institutions in Hughes laboratories. In a complementary program at HHMI's Janelia Farm Research Campus in Loudoun County, Virginia, leading scientists are pursuing long-term, high-risk, high-reward research in a campus specially designed to bring together researchers from disparate disciplines. The Institute's biomedical research expenditures during fiscal year 2008 totaled $658 million.

HHMI researchers are widely recognized for their creativity and productivity: 124 HHMI investigators are members of the National Academy of Sciences, and there are currently 13 Nobel laureates within the investigator community.

The Institute also has a philanthropic grants program that emphasizes initiatives with the power to transform graduate and undergraduate education in the life sciences. Additionally, it supports the work of biomedical researchers in many countries around the globe. Through aggregate investments of more than $1.2 billion, the Institute has sought to reinvigorate life science education at both research universities and liberal arts colleges and to engage the nation's leading scientists in teaching. HHMI grants totaled $83 million in fiscal year 2008.

The HHMI endowment is reported on an annual basis and stood at $17.5 billion at the start of the current fiscal year on September 1, 2008. Its headquarters are located in Chevy Chase, Maryland, just outside Washington, D.C.

Here is my summary of their diverse research areas:

• prevent malignant T cells from reaching the nervous system
• use computational methods to create an equivalent cartographic approach for molecular biology
• investigate how the enzyme that builds telomeres, telomerase, is created and controlled
• remodel of the normally rigid and highly ordered cytoskeleton so that a more flexible framework can take its place
• investigate how chromatin helps stem cells decide when to commit to developing into a particular cell type
• determine why each lake harbors a distinctive community of parasites. and then measure how sticklebacks' immune systems have evolved to fight off the parasites found in any given lake
• discover and biosynthesize small molecules that might be useful medicinally
• build a synthetic replacement for CFTR
• define the rules that determine noncoding RNAs' structure and activities
• understand how these genes regulate development in different vertebrates, and illuminate the origins of these disorders
• explore whether Hox proteins in interneurons and sensory neurons, which control motor neuron firing patterns and transmit feedback about muscle action, help assemble the complete circuits that control walking and running
• unwind the complicated molecular pathways that control the degradation of HMG-CoA reductase
• provide deep insights into how brains work—and what goes wrong with specific neural circuits during illness
• reveal how the signals triggered by these receptors are processed as they travel from the skin to the spinal cord
• lead to regenerative therapies that do not require stem or progenitor cells
• make ready quantities of disease-specific cells to help researchers be able to study the roots of the disease process and speed drug discovery
• catalog all of p53's actions and how those actions vary in different cell types and under different conditions
• know exactly which glial genes are involved during trauma — an important consideration in designing potential therapies for spinal and nerve injury and neurodegenerative disease
• dissect the genes that control insects social communication behaviors
• focus on a class of channels that passively transport glucose through the cell membrane
• gather new information about how mismatch repair proteins move along a DNA strand during the course of a repair reaction
• improve stem cell models for studying development and disease
• study steps of homologous recombination
• study the genetic programs that control the formation of memory T cells and bestow these stem cell-like characteristics on T cells during infection
• use structure to understand how the RNA works, explore the structure and evolution of additional RNAs that other viruses use to manipulate their hosts in a myriad of ways
• unravel how microbes contribute to human health and disease—in particular, obesity, inflammatory bowel disease, and malnutrition
• determine how feedback loops and other design features link signaling molecules in elaborate molecular circuits
• reveal the exact shape of the molecules that build telomeres and keep them intact
• study the causes and consequences of these genetic conflicts in yeast, fruit flies, and primates
• build evidence that many microRNAs are themselves oncogenes and tumor suppressors
• help determine how that neural circuitry fails in people who have attention-deficit/hyperactivity disorder
• learn how injury stimulates new growth and how new cells correctly integrate into tissue that is being repaired
• find the factors that control the parental chromosomes shuffling and understand how they differ among individuals
• know what is in the planarian's tool kit that explains its remarkable regenerative feats
• address how these remarkably flexible networks transform over different time scales — from rapid adaptations in response to changing nutrient availability to evolutionary changes in metabolism that have occurred over 300 million years
• find out whether the pathogen or the host truly controls latency
• understand how the brain distinguishes different tastes and how perceptions of taste can be modified by experience
• explore the critical connection of a key hunger circuit and tease out the precise role of each component of the signaling pathway
• learn exactly how Histoplasma infects and multiplies inside macrophages, the scouts of the immune system
• get right down to the single-molecule level to find out what happens when DNA helicases — molecular motors that drive DNA repair mechanisms — find problem locations in the genome where their activity is needed
• use cells engineered with a cancer-causing mutation and identical cells lacking the mutation, and then both cell lines are treated with chemicals to find selectively lethal drug candidates
• discover the elusive molecular machinery that performs both the guiding and unloading functions of vitamin A
• study the role of DNA repair in promoting drug resistance in cancer cells
• revealwhy the molecules that drive our endocrine system are built as they are and provid new ways of understanding how variation in their sequences and structures affects their functions
• study the biochemical mechanism of rhomboid action and its biological function in a diverse range of organisms
• study blood-forming and muscle-forming stem cells
• study how genetic information is translated into the forces that move tissues during development
• find out how molecules in air alert animals to danger, food, and potential mates
• see the protein machinery in fine cellular structures as they move and act to enable learning and memory
• understand how cells in a developing organism coordinate their movements to define the shape and structure of tissues and organs

I am holding my breath and watching ......