David Baltimore talks AAV

GAINESVILLE, Fla. – 1975 Nobel Prize winner and HIV pioneer David Baltimore was the keynote speaker last Wednesday at the Florida Genetics 2012 Symposium. The program this year was dedicated to University of Florida’s Kenneth Berns, the father of adeno-associated virus therapy. Baltimore’s presentation, “AAV to the Rescue,” reflected the great strides research has achieved since Berns’ initial studies on the virus at the UF Genetics Institute.

Baltimore began by describing the unique problems HIV presents to human immune systems and vaccination attempts.

He said that despite its reputation, HIV is “not a particularly powerful virus.” He noted that it can take a hundred instances of unprotected sexual contact for infection to occur.

What HIV lacks in potency it makes up for by being extremely elusive to the human immune system, primarily because the virus is unaffected by most human antibodies. This is due to a thick outer carbohydrate layer, a binding site inaccessible to most antibodies and an additional binding site that is only accessible after the virus has already infected immune system cells by way of CD4 receptors. HIV also mutates quickly, requiring any vaccine attempts to be especially potent.

Years into the HIV pandemic, researchers were finally able to identify antibodies capable of fighting the virus on a broad scale, and while they were discovered too late to protect their hosts, Baltimore said they are the source of much of the current HIV vaccine research.

“…By that time, the people who make them have so much virus in their system that they can mutate against any antibody that come along, even the best,” Baltimore said.

However, the logistics of producing and dispersing the capable antibodies in viable quantities, especially in the developing countries where HIV is pandemic, are nearly insurmountable. Baltimore’s research focuses on leveraging specific genes from these antibodies so that the host body will produce vaccine-level amounts itself, a process called vectored immunoprophylaxis (VIP).

The key to the process is the family of adeno-associated viruses. Berns was the first to utilize its unique qualities that now make it a gene therapy leader. The virus is harmless to humans, has long-lived expression from a single administration, expresses inserted genes strongly and is already present in about 80 percent of humans. Its only drawback is a small genome, only about 5000 bases to humans’ 3 billion, which limits the size of genes it can carry.

Baltimore’s lab chose a strand of AAV in which to insert the genes necessary to produce b12, one of the HIV antibodies. The altered AAV was injected into the muscles of mice, which began to produce b12 in copious amounts for an extended period of time. Mice, genetically modified to have immune systems similar to humans, were injected with the AAV and then unnaturally large doses of HIV before weekly monitoring of their CD4 levels.

The presence of HIV is indicated by an almost immediate drop of CD4 counts in the blood. Mice injected with the AAV maintained or increased their CD4, demonstrating the potency of the process. The b12 antibodies are only effective against a limited number of HIV strands, however, so their genes were soon replaced in the AAV by another, VRC01, which is effective against almost all known strands.

Following the conclusion of their study in January, Baltimore and his team have continued to explore the possibilities of VIP. They tested it against HIV strands with slightly different mechanics and delivery through a mucosal membrane, its normal transmission method. All experiments found the VRC-type antibodies produced by modified AAV extremely effective in protecting mice against HIV.

With extensive experimental data to support it, the VIP process is transitioning to clinical development in humans. Although it is cheap and stable, Baltimore had to find a way to reverse the production of antibodies in patients in the case that they responded to them detrimentally. Using a Cre-Lox process, he was able to overcome limits set by AAV’s small genome to successfully stop the antibody’s production.

“The cost for us to make a batch of virus for clinical tests is enormous,” Baltimore said. “But I can only imagine that if we had a mechanized process to make virus that the yield from cells is so enormous, that we could make it at quite a reasonable cost.”

Baltimore said VIP can work for other viruses as well. Due to the rapid mutation of HIV once it is established in the immune system however, he believes it is unlikely that VIP can be used as a cure.

Working to make tomatoes tastier

Last week, researchers from UF’s Institute of Food and Agricultural Sciences discovered an enzyme that makes tomatoes better flavored for consumers.

The enzyme, dubbed CXE1, is produced by the fruit as it ripens. Its role is to inhibit the production of acetate esters, chemicals that ruin the taste of tomatoes in consumer studies.

The researchers, led by Harry Klee of the UF horticultural sciences department, are looking for a few key enzymes that can be manipulated through the breeding or genetic modification of tomatoes. Klee believes CXE1 could be one of those few, according to the press release.

This isn’t the first time UF has contributed to making tastier tomatoes. The Tasti-Lee tomato line was developed with the help of the university.

Floridians optimistic about economic recovery

The monthly evaluation for October by UF researchers has found that Floridians are breaking post-recession records for overall positive outlook on the economy. However, in regards to their personal finances, the state is still down. Confidence in personal finances compared to last year are down 3 points while confidence in their position a year from now dropped by 2 points.

It’s an important outlook just a few days before election night, where post-recession confidence bodes well for Obama. Chris McCarty, director of UF’s Survey Research Center, attributed the falling personal finance confidence to the presidential debates and the upcoming “fiscal cliff” – when poorly-looked-upon federal budget cuts and tax increases will be decided unless Congress approves another procedure.

This month’s results can be found here at the Bureau of Economic and Business Research.

Invasive lionfish may be here to stay

University of Florida researchers have spent the last year conducting a study on the process and costs of removing the invasive lionfish species from Florida’s waters. The result is less than stellar: control can only be kept in specific, targeted areas and with lots of manpower.

The lionfish eats a lot, and has an appetite for native Florida sport and food organisms like grouper and shrimp. It’s gradual spread into the Gulf of Mexico is worrisome, as there are many seagrass nurseries that could be devastated by a large lionfish population.

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The researchers used derbies, essentially free-for-all lionfish fishing periods, for divers and snorkelers. They then studied the derby results and the effect they had on lionfish populations.

What they found was that extensive fishing produced smaller lionfish. While that’s a good sign for grouper, who are vulnerable to the larger lionfish, it could be a threat to the shrimp populations.

This is just one in a string of stories about the effects of invasive species on Florida plants and animals, including those of the Burmese python and kudzoo plant.

2013 National Association of Science Writers conference will be in Gainesville

 

This is looking forward a bit, but the National Association of Science Writers will be hosting its main conference of 2013 at the University of Florida. The conference will expose many University of Florida museums and laboratories to all levels of science writers, as well as host a number of talks by UF researchers and lecturers. Expect some great updates and photos here in addition to me live tweeting of events @APKays

Satellite imagery used to study remote ecosystems

Remote ecosystems provide a number of obstacles for researchers wishing to study them — that’s why they’re still remote. Moving and maintaining equipment, limited low-impact observation methods and accurate controls are just a few examples. 

A team of researchers, including Matteo Convertino from the University of Florida’s Institute of Food and Agricultural Sciences, have developed software that utilizes satellite photos of an area to determine a broad range of observations.

Convertino is helping the team make better use of the images, according to the press release.

“There’s currently not a lot of satellite imagery used in ecological studies,” said Convertino, with UF’s agricultural and biological engineering department. “Part of the reason is, there’s a strong need to improve mathematical formulas for analyzing the data, and that’s what we’re doing here.”

Their current system uses light frequencies to find the number of plant species in an image, where they were and how many of each were in the area.

The method is being used in other areas too, from microscopic stem cells to the analysis of soil and water by satellite. 

Obviously these kinds of discoveries have extensive use in science, but I’d also be interested in its use for human population studies. Demographic measurements of busy pedestrian areas, such as theme parks, could be pretty useful.

Soil variability provides challenges for storing carbon

Many types of soil lack carbon, and are being looked at as a possible treatment for climate change. The process of taking carbon out of the atmosphere and putting it elsewhere is called carbon sequestration. Some landowners could make money in the future by sequestering the carbon from government or private industries in their soil.

However, according to a study put out by the University of Florida on October 22, Florida’s soil makeup has a patchwork arrangement. The patchy nature of the soil in regard to the amount of carbon it contains makes it difficult for large-scale carbon sequestration in an area.

Beyond climate change implications, soil carbon is an important factor in agriculture. It plays a significant part in the soil’s quality and that of the plants growing in it, and is therefor helpful for farmers. 

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