At HWI, our scientists seek to discover the fundamental causes of disease and to lay the foundation for new and effective therapeutic approaches.  Their basic research can be likened to a long-term investment program.  The benefits may not be realized immediately, but ultimately they will have a profound effect on the health of future generations.

What causes disease?

Our bodies are made up of cells that contain many different types of molecules.  Proteins are an extremely important type of molecule found in our cells because they perform many essential functions.  For example, proteins digest our food, carry oxygen around in our blood streams, and make our muscles move.  The instructions for making proteins are contained in the DNA sequences that comprise our genes.

Very broadly speaking, there are two types of diseases.  In the first type, a person is infected with bacteria, a virus, or some other kind of pathogen.  These intruders grow in the human body and alter its normal state leading to illness. 

In the other type of disease, a human protein "misbehaves" in some way.  Although all humans have the same types of proteins, some of their proteins may differ slightly because of individual genetic differences.  Occasionally, some of these differences result in variants that do not function properly, and this also leads to disease.

What do drugs do?

Drugs are molecules that interact with proteins and change their activity.  Drugs can be used against the two types of diseases with alternative strategies.  To treat an infection, a drug can take advantage of differences between a bacterial or viral protein and the corresponding human protein.  For example, a drug can selectively block the activity of a bacterial protein thereby killing only the invading bacterial cells while leaving the cells of the human host unharmed.

On the other hand, if something has gone wrong with a normal human protein, a drug may be used to change how this protein works.  Often, a drug can block an overactive protein to limit hyperactivity.  Alternatively, a drug can trick a "sluggish" protein into acting when it otherwise would not.  In this way, a disease-causing protein is made to act like a healthy one.

Why is HWI research important?

The majority of the work at HWI is undertaken to determine the molecular structures of proteins that are drug targets.  If we can find out what a protein looks like, we have a better chance to figure out how existing drug molecules interact with it.  We can then try to identify new sites on the protein molecule where a new drug might be designed to bind to it, possibly altering its activity.

HWI scientists also study the normal function of important proteins in order to gain a fundamental understanding of a biological system.  This is critically important. If we do not understand what a particular protein does in a normal cell, we will never understand what goes wrong in a disease state.

How do other people learn about discoveries at HWI?

After scientists complete an experiment, they publish the results in scientific journals.  Prior to publication, each article is reviewed by experts who can recommend accepting, rejecting, or revising a paper.  Other scientists who read the published papers can build off the HWI research in their own research efforts.

HWI scientists are part of a larger community of researchers at universities and research institutions across the world.  Each publication is an advance that allows new understanding about biology and health, as well as a new understanding of what can go wrong.

Who pays for all of this?

In the United States, the federal government supports basic research through agencies like the National Institutes of Health (NIH), the National Science Foundation (NSF), the Department of Energy (DOE), and the Department of Defense (DOD).  Elected officials realize the fundamental benefit to society that comes from basic research, and pharmaceutical companies alone cannot support efforts of the magnitude that are needed.  Not every good idea will result directly in clinical advances.  However, even in many of these cases, insights will be provided into biological processes in ways that could not be predicted. 

Scientists at HWI compete with scientists around the country for federal research dollars.  Historically, our scientists themselves have raised the largest portion (> 85% in fiscal year 2008) of their funding by applying for research grants from NIH and other federal agencies.  Grants awarded by NIH have been thoroughly reviewed by other scientists (a process known as peer review) to ensure that the most worthy projects are supported by tax dollars.  Over the years, HWI scientists have been very successful in obtaining grants — a tribute to the quality of work performed at the Institute.

The rest of HWI's support comes from private charitable foundations and individual contributions that help to initiate new projects or to move an existing project in a new direction.  Such funds are absolutely vital since federal grant proposals require preliminary evidence that the proposed research will succeed.  These smaller research funds are used to obtain these preliminary results.

LEARN MORE

HWI research projects all fall into the category of structural biology.  To learn more about the science of structural biology, explore the other links in this section or go to http://publications.nigms.nih.gov/order to obtain a free copy of the publication, The Structures of Life, available from the National Institutes of General Medical Sciences, a component of NIH.