Five scientists from different disciplines pool their knowledge to fight AIDS in tiny but effective way
Nanotechnology isn't as complicated
as it sounds. You just have to think small. Really, really small. Then even smaller than that. If you can wrap your mind around it, think in the range of one billionth of a meter. That's about the size of 10 hydrogen atoms lined up. It takes about 1,000 of these nanometers
to total the diameter of a typical biological cell.
That's so small that it requires a whole new set of tools just to investigate this teensy biological frontier and a whole new vocabulary
to describe it. To name just a few of the terms coined by this study of the infinitesimal, there are nanoparticles, nanocrystals, nanoplatforms, nanomaterials, nanografting, nanofabrication, nanophases and, researchers hope, nanotherapy.
It's this latter possibility – nanotherapy – that has captured the attention of a group of basic scientists at UC Davis who come from faculties of the School of Medicine, the College of Letters and Science and the School of Engineering. These five researchers – incidentally all women – and their labs are hoping to use synthetically engineered nanoparticles as a decoy that would block the human immunodeficiency virus that causes AIDS from infecting human cells.
This is no mean feat.
Worldwide, the HIV epidemic is showing little sign of abating. By the end of 2001, 40 million people were carrying the virus: 940,000 in America. While most of those infected in America can trace their infection to the use of illicit injectable drugs, internationally its primary cause is clear: unprotected sex.
Medical research has made great strides in treating HIV infection, but its toll continues to astound the epidemiologists who total the numbers. Just last year, 3 million died from HIV; 1.1 million were women and more than a half a million were under the age of 15. Ninety-five percent of the 40 million living with HIV are in developing countries. In sub-Saharan Africa, for example, 28.1 million are infected with HIV – numbers that threaten the very survival of whole nations.
Among the hotbeds of AIDS research, UC Davis holds a prominent position. As early as the late '80s, UC Davis researchers had already identified simian and feline immunodeficiency viruses whose similarities to HIV greatly advanced understanding of retroviruses. Now, under the auspices of the Northern California Center for AIDS Research, headed by medical school virologist Satya Dandekar, an ambitious collaboration among three chemists, a chemical engineer and material scientist and Dandekar is poised to make further important breakthroughs in understanding and, perhaps, preventing HIV infection.
This collaboration, funded by a National Science Foundation grant that encourages interdisciplinary basic science research, features principal investigator and chemistry professor Jacquelyn Gervay-Hague, associate chemistry professor Gang-Yu Liu, chemistry professor Susan Kauzlarich, associate chemical engineering and material science professor Marjorie Longo, and Dandekar, professor and chair of the medical school's Department of Medical Microbiology and Immunology. Together with the students and fellows in their labs, the women have formed the Nanoscale Interdisciplinary Research Team.
'We are targeting our study at the way the virus infects the cells that line the mucosal membranes of the rectal and vaginal tracts," said Dandekar, who has been investigating the mechanism of mucosal infection and immunity since joining the medical school in 1983 following a post-doctoral fellowship at the National Institutes of Health. "That is clearly the most common way HIV is transmitted, even though most Americans seem to contract the virus through IV drug use. But if you want to really attack the spread of this virus, these mucosal membranes have to be the target."
Like all viruses, HIV carries proteins on its surface. One of these – GP120 – recognizes and binds to a component of the surface membrane of the mucosal cell it is targeting, specifically the carbohydrate molecule known as Galacosyl ceramide, or Galcer, for short.
"That interaction between GP120 and Galcer
can either be a weak interaction or a strong one," said Longo, the chemical engineer on the team. "Part of our quest is to understand how you get one or the other."
To explore this attachment
of GP120 to Galcer, the UC Davis scientists are manufacturing synthetic nanoparticles that are covered in specific numbers of Galcer molecules. The diminutive particles can vary not only in the quantity of Galcer present but also in its mobility. By determining which Galcer-laden nanoparticles are the most attractive to HIV, the researchers believe they will be able to create a particle so tantalizing to HIV it would, if given the choice, choose the synthetic particles rather than the mucosal cells to infect.
"This is a project," said the medical school's Dandekar, "that combines and uses modern technology to study very basic science questions that have the potential to answer important clinical needs. We believe that by focusing on this very important first step in the infection process, we can block its ability to enter the cell and wreak havoc.
"But I am not a chemist or an engineer. I am a virologist. I know how to grow virus, infect cells, manipulate viral genomes and study all the effects viral infection has on host cells and hosts in general. I have a very good understanding of what it does to cause AIDS. But I have no idea how to put nanoparticles
together. I can't make the decoys. I can't image them. I can't manipulate them. So I need the work these other researchers are do ing. I provide the biological model – the human cells – that can test the efficacy of their work."
Indeed, it is this total collaboration,
as Dandekar so aptly calls it, that distinguishes the work of these five UC Davis faculty women and their respective labs.
"We bring deep and diverse experience to this project," said Dandekar. "But there is no way that any one discipline alone could do the work of this project. We each need the others."
Already having achieved promising results, the group expects to publish within a year and is hopeful that their synthetic Galcer nanoparticles could be added to such commonly available products as petroleum jelly.
"We know that to control the spread of HIV infection we need both good educational outreach and the availability of easy-to-use, readily available preventives that can block infection," said Dandekar. "We believe this approach may fit that bill.
"We also believe that through this collaboration, which we expect will continue beyond the four years of this first grant, our approach will be applicable in other mucosal infections, such as E.coli, salmonella and Valley Fever."
Principal investigator Gervay-Hague is also excited because the interdisciplinary collaboration is giving the graduate students and fellows in all five of the labs the opportunity to learn about other disciplines.
"It really is an extremely rich environment for the young scientists who are working on this project, particularly the students," she said. "It's the advantage of five completely different labs coming together to work on the same problem and it will prepare them well for the future."