Center News

The following is a transcript from a discussion with Thomas A. Reh, PhD, Professor of Biological Structure and Principle Investigator examining Retinal Development and Regeneration, joined by Catherine Ray, Reh Lab Project Manager. The objective of the discussion was to learn details about the research the laboratory will be conducting and what resources the WaNPRC would be providing to support it. They were also joined on the phone by WaNPRC administrator of program operations Jesse Day. The project we discussed is pursuing regenerative therapy for glaucoma which is one of the National Eye Institute Audacious Goals. 

The Basics

Catherine Ray: First group of six animals is a cohort to set up the glaucoma induction model.

Tom Reh: There are going to be two phases. There is a guy at Vanderbilt, David Calkins, who’s been working on a glaucoma model in squirrel monkey (Saimiri sciureus). That was the idea was that we would go learn from him how to do it. And then we would bring that surgical technique back here. So that is the first phase.

CR: We’re not quite sure at this point what the training will entail.

TR: Our surgeon, Jen Chao, is in charge of doing that. She’s an MD, PhD in the Department of Ophthalmology here (at the University of Washington). She will be responsible for learning about the actual injection. Basically, the procedure is fairly straightforward. Glaucoma is normally caused by an increase in intraocular pressure. This is basically pressure within your eyeball. And that is partially due to either a congenital or acquired blockage of the aqueous humor’s (the clear fluid filling the space in the front of the eyeball) outflow tract. So your eye’s constantly making new fluid and that fluid is supposed to leave the eye through this outflow tract. When that is blocked or constricted, often people have really strong myopia (nearsightedness). They have problems with that because the eyeball is of a shape that it constricts that.

But anyone can get glaucoma, if you have intraocular pressure increase, and then what happens is the cells in the retina die. A certain class of cells degenerate. These are the ganglion cells. As so what you do when you try to induce this is that you actually inject into the anterior part of the eye, where the aqueous humor is located- little microbeads and then those actually plug up the tract. And so now because the tract is plugged up by these little microbeads, the intraocular pressure goes up, creating glaucoma. It’s actually not that hard to do. Somebody figured out how to do this so it would work and they have done it already in a bunch of different animals, and Dr. Calkins does it in squirrel monkeys and it works. It takes a couple of months to get glaucoma. To get the pressure up and have it elevated over a long enough period of time to create the glaucoma. In mice you can do this and it happens much more quickly, but in monkeys it takes a longer period of time.

Induction of Glaucoma

TR: Project will be in two phases. The first will actually be giving the monkeys glaucoma. And so, the NHPs will be injected with tiny little microbeads into the anterior of the eye which block the output tract. This causes intraocular pressure. A group down in Vanderbilt led by David Calkins has worked this out.

It’s been done in a lot of other animals before but it hadn’t been done in squirrel monkey. He figured out a way to do it. Dr.Chao is a retinal surgeon on humans, and she will do the surgery on the monkeys. It involves injecting these beads into the anterior of the eye. She’s working with Vanderbilt and learn from David Calkins’ surgeon. She’ll then reproduce those injections here. And we we’re thinking that could go on in the first year. That’s what our timeline would be.

CR: Six animals would establish the model here in Seattle after Jen Chao learns from Vanderbilt to see how it’s done. Making sure that we could recapitulate it here.

TR: And so, I think we said six. Six would be ideal. We could do fewer than that. I think it’s gonna be simply reproducing what’s already been done at Vanderbilt. Other monkeys, we would do the next phase of the project, because we’re causing intraocular pressure cause the death of the retinal ganglion cells, which are the cells that convey the message from the eyes to the brain, those cells die from the intraocular pressure increase. And so, what we want to do is see if we can replace them. And so we can get human embryonic stem cells (ES Cells) to make ganglion cells pretty well. We have a human embryonic stem cell line that actually makes these ganglion cells red. Then we can track them with a fluorescent RetCam imaging, and so what we proposed for the next cohort of animals was actually to just try some of these transplants.

CR: Yeah, in the second part of the experiment. The first trial we’re just doing the cells with the glaucoma induction with another cohort. If that works, there are various other experiments that would involve keeping the monkeys for longer a term. We would collect eyes for electrophysiology, etc.

TR: We’ve done injections of human embryonic stem cells into monkeys before, which is one of the reasons why I think that the NIH reviewed our grant positively. I think we’re the only ones in the world who have injected human embryonic stem cells into squirrel monkeys, and one of only three groups to every inject them into any monkey’s eye. So, we reported that in a publication last year. Basically what we did was a sub-retinal injection of embryonic stem cells. It was several years ago when we did this. We don’t think we’re going to immunosuppress this time, but there will be local (intraocular) immunosuppression at the time of the surgery, because they are human cells going into a monkey.

We also proposed, as a worst case scenario, we would derive monkey cells, but we don’t have a squirrel monkey yet. So we’d have to almost make a squirrel monkey IPSL. I know Eliza Curnow here has embryonic stem cells from macaques. That one is closer than human. The other option is that we can engineer the cells to not have T-cell receptors, and they in theory would not get rejected. There is a company in Seattle, Universal Cells that’s doing that for potential human transplants.

So I think those are some options. But I think right now, we’ll probably keep it simple. So we hope the money comes within the next couple months. That’s the idea. There is going to be a regular review by the review panel advisory board for these U grants and we’re meeting with ours on February 5 at the NIH. After that we’ll nail down the timelines and milestones.

Over the next year, it will be six squirrel monkeys.

Nuts and Bolts

CR: We would want to purchase any monkeys until after that takes place. 36 over the course of three years. No more than 6 at a time.

TR: I am pretty sure that we can accomplish what we need to with less than that.

Jesse Day: Please keep me apprised of timelines as you know more.

CR: I had sat down, just really quickly with Animal Trainer Kelly Morrisroe, to talk about behavioral training and she brought this up as well. I don’t think we have a preference as far as sex goes. I think we’re supposed to be keeping it balanced for the NIH.

JD: Evenly distributed as much as possible (for validity).

CR: Based on availability, we don’t care about the sexes of the animals too much.

TR: House females together more so than males?

CR: Males could be fixed if necessary. I think the way the grant is written, these are all three to nine-year-olds. A little bit more mature age range.

TR: I think in terms of access to the surgery suite and anesthesiology, etc., the way we ran it last time was pretty straight forward. I guess we’ll have to book those sorts of things ahead of time. I remember that Jen was able to bring over a microscope and a RetCam imager from Ophthalmology. Is there an operating microscope available and any kind of device for intraocular imaging?

JD: I would bet that was their equipment that they brought in…. contact the surgery group. That was probably the last study to use it.

TR: I know the Neitz study was doing viral injections. Those are being done here in the I-Wing, correct?

JD: They’re are using the RetCam for that. Talk with the Neitz group about that.

TR: Ok, I think that would be a good idea, we can coordinate and piggy back on top. Again, Jen Chao does the injections for the Neitz group, so she can figure out where everything is. We have an EE protocol? Is that something that the Primate Center takes care of that?

We need to be able to take the intraocular pressure. Once they’re anesthetized, it’s difficult to do because the intraocular pressure declines so you can’t get an accurate reading. So it could be that we would need to train the animals to hold still while we give them a puff of air on the eye.

CR: I sat down and had a meeting with Kelly Morrisroe and she seemed to think that was feasible. According to her, we might even be able to pre-screen some of the monkeys to see if they might be predisposed to receiving behavioral training. That may be a bridge that we need to cross as we get a little bit closer to ordering the monkeys. It seems in terms of our timeline right now, it would be until February that we would even be ordering the animals.

TR: If that is something that your broker can screen animals for. One of the reasons that the Neitzes used squirrel monkeys was that you have this. The males don’t have color vision but the females do, and so by introducing another opsin pigment into the males, they were able to get them to see color.

The other attraction is their eyes have a fovea (a small depression in the retina of the eye where visual acuity is highest. The center of the field of vision is focused in this region, where retinal cones are particularly concentrated).  But the animals as a whole aren’t as big as a macaque, which is appealing. The eyes are a good size for surgeons to do their manipulations. Part of why we’re doing this project, there aren’t that many animals that have foveas other than primates, so the work has to be done in nonhuman primates. Other animals can’t focus on the detail like humans and monkeys can. Part of what happens with glaucoma is you lose that sharp vision. So we are trying to restore that ability to see fine detail that is only found in primates.

Stanford is coordinating the project. Johns Hopkins is probably the best in the world at making the stem cell into the ganglion cells. Jeff Goldberg is one of the best people in the world for his studies on regeneration on ganglion cells in mice. Part of this was to also find ways to stimulate the ganglion cells to grow into the brain. It doesn’t do any good if they just stay in the eye. They have to grow accent all the way down the optic nerve, to the brain, which is a long way.

Rigor and Reproducibility

TR: I think the thing about reproducibility, is you gain a lot when three or four labs are involved, because essentially we’re going to be carrying out the same experiments at three different sites. And if we don’t get the same results, then we will have to figure out why that is.

I think part of the problem with reproducibility in science right now is that some of the conditions that make these experiments work are not completely defined because we’re always doing new things. It’s not like we’re doing the same things over and over again. Scientists basically do new things all the time, that’s what they do. So when you do new things, you don’t always know all of the variables that need to be controlled to get it to work. It just happened to work for you in that particular set of conditions and variables, etc. That’s particularly difficult when you talk about the small ends that you have. The small numbers of animals or experiments that you’re able to conduct in primates, and so I actually think in mice, you can do 30 mice and it’s no big deal. If someone does another study in 30 mice and they get a different result, you can figure out pretty quickly what those variables were from site to site. For large animals, you’re not gonna get that chance, so I think doing the experiments at the three sites at the same time, at least we’ll be able to identify the variables between sites as potential sources of irreproducibility. That’s one of the best things about this. It’ll allow for kind of instant reproducibility.

We’ve got some of the best labs in the world that are our collaborators so I figure they have been rigorous up to now.

CR: These are some of the only groups who have ever done this work before. I don’t think anyone else is doing this glaucoma induction model anywhere else.

TR: No, and so in a way, that’s going to validate that model right away. If we can’t reproduce Calkin’s model here, the project can’t move forward. That’s kind of high stakes reproducibility right there. Also remember that we have a scientific review board that’s basically going to look over our work every six months. They’re gonna ask, “How are you folks doing? What’s going wrong? What’s the progress?” t’s still exploratory science in that we really don’t know if these ganglion cells are going to survive the transplantation or not be rejected. Find the right layers. Make the right synaptic connections with their partners. Grow their accents in the brain. I mean, this is a tall order and I doubt we’ll reach all of our goals in five years.  I think that the progress that we make will at least define what the things are that we need to work out. I see this as kind of sending us around to the move to see if we get back and what happened along the way before we actually land somebody there. It’s certainly not that historic, but nevertheless, it’s about that complicated.

Audacious Goals Initiative

TR: I think this whole initiative by Paul Sieving of the National Eye Institute has been his big push over the last five years. The point of it is to see if we can, rather than just stopping the eye from degenerating, but to repair it. You know, it is restoring vision back to what it was before someone got a disease or injury. So that’s the whole thing. How can we do better than simply halting the disease, but how can we reverse it. That’s audacious! We don’t do that for very many things.

Potential Setbacks?

TR: Sometimes you find that when you do an experiment, you get positive results but it didn’t turn out exactly how you had planned. So for our work that we did in the squirrel monkeys before, we were hoping to transplant rods and cones (Rods are responsible for vision at low light levels (scotopic vision). They do not mediate color vision, and have a low spatial acuity. Cones are active at higher light levels (photopic vision- daylight or other bright light), are capable of color vision and are responsible for high spatial acuity).

We didn’t see any rods and cones in that paper. What we did see were ganglion cells. So the PI of this grant, Jeff Goldberg watched a seminar that I was giving two years ago when I presented some of this. He described it as when you got lemons, make some lemonade. Because you didn’t get photoreceptors integrated into the retina after your transplant, don’t feel so bad. He was interested in glaucoma (a disease that damages your eye’s optic nerve). So that study basically led to this grant. We now have a better idea that we’re more likely to be successful with ganglion cells. So rather than treat macular degeneration, now we’re going to try glaucoma which is a disease of the ganglion cells and not the photoreceptors.

I think in general, we scientists are pretty opportunistic. If we see that the approach that we were taking isn’t really working out as well as we had hoped, then we try something else. In some ways, the science that gets translated into medicine is the science that works over and over again and is successful. This is complicated stuff that we are doing but if it actually works, then I’m sure it will be translated into medicine.

Human Embryonic Stem Cell controversy

TR: One of the postdocs in the lab who will be the primary person growing the stem cells for this project, came to us from Indiana. In Indiana, they’re not allowed to do research on human embryonic stem cells. She did all of her work on induced pluripotent stem cells (Induced Pluripotent Stem Cells (iPS) iPSC are derived from skin or blood cells that have been reprogrammed back into an embryonic-like pluripotent state that enables the development of an unlimited source of any type of human cell needed for therapeutic purposes). So you can create stem cells that are very much like human embryonic stem cells. For her graduate work, she had to work entirely with iPS Cell because they weren’t ES Cells. On the other hand, IPS Cells are a little bit trickier to work with, so it made her a much better scientist actually. Now when she works with ES Cells in Washington, which she can now do, she says, “Well these things are really easy.” In the end, it’s a work around. IPSCs I think provide a very straight forward alternative to ESCs and one that is as successful. In fact, I think in general, the field is moving toward IPSCs because ethically, it is much simpler and they’re not that much different. They’ve been proven to be almost identical.

NHPs in Research

TR: There is controversy around the use of nonhuman primates and some people are putting pressure on lawmakers to reduce it. We’re aware of that. These are really bad diseases for people to get. Glaucoma, macular degeneration, and loss of sight. It’s serious stuff. It justifies to us, our use of the monkey model and stem cells. We feel that these are experiments that can’t be done in any other animal or in any other way. The fovea is really quite unique to primates, and that is kind of where we have to work.

 

 

 

 

 

 

 

 

 

Staphylococcus aureus (S. aureus) is a ubiquitous bacterium colonizing 20–30% of the human population. Beyond asymptomatic carriage, S. aureus causes a wide range of infections, such as skin and soft tissue infections (SSTI), bone, joint and implant infections, pneumonia, septicemia and various toxicoses such as toxic shock syndrome. Shortly after the introduction of penicillin in the 1940s, the first penicillinase-producing S. aureus strains were detected, leading to the development of the penicillinase-resistant semi-synthetic penicillins such as methicillin, oxacillin and the first/second generation cephalosporins, the drugs of choice for treatment. Within a year after the introduction of these drugs, methicillin-resistant S. aureus (MRSA) were reported which made them useless for treatment. MRSA has become a serious international problem. Some strains predominate in geographically restricted settings while others have achieved pandemic spread. Some are associated with humans and others primarily with animals.

In the hospital setting, MRSA often contaminates surfaces and is responsible for hospital-related deaths [~11,000 deaths in 2017].  However, the number of MRSA cases in most hospitals are going down as they do a better job of preventing transmission from patient to patient using a variety of methods to reduce transmission within the hospital. These include good personal protection equipment, bathing with chlorhexidine, and increasingly using ultraviolet (UV) robots for deep cleaning. All of which have helped reduce the transmission within the hospital.

While practices to reduce MRSA cases in hospital populations are improving, a new study has focused attention on the human/animal interface out in the environment. Wild animals harbor and are potential reservoirs for MRSA, according to a study published earlier this year (May 1) in the FEMS Journal of Microbiology Ecology (https://academic.oup.com/femsec/article/94/5/fiy052/4950395). The study identified MRSA in rhesus macaques (M. mulatta) along with domestic swine herds from the Kathmandu valley in Nepal.

The lead author is Dr. Marilyn C. Roberts, Professor of Environmental and Occupational Health Sciences in the School of Public Health, and Affiliated Scientist at the Washington National Primate

Research Center (WaNPRC) at the University of Washington (UW), describes the interaction between the humans and monkeys around temple sites in Nepal. “These animals in Katmandu are attracted to people. It’s sort of like ducks along the lakefront here in Seattle. When you walk there, the ducks think they’re going to get fed. Similar to this, the monkeys at these sites equate people with food,” Roberts said.

Researchers surveyed 59 rhesus monkeys. Utilizing and adapting a non-invasive saliva sampling technique, UW Research Professor and WaNPRC Core Scientist Randy Kyes and his Nepali team at Tribhuvan University distributed sweetened pieces of oral swabs for the wild monkeys to chew on. Once the animals had discarded the swab, the team retrieved the samples and sent them to the laboratory in Nepal where the MRSA strains were isolated.

Of the macaque samples tested, 6.8% were positive for MRSA, with three of four macaque MRSA isolates identified as ST22 SCCmec IV. A more recent sampling found four more primate ST22 SCCmec IV. Some of the recent environmental samples were also ST22 SCCmec IV. ST22 SCCmec IV is normally considered a human strain and this study suggests that humans in Nepal are sharing their strains of MRSA to both domesticated swine population, which also carried the same ST22 SCCmec IV, as well as the wild macaque populations. We know that this strain (ST22) is found in humans in Nepal and is also very common in Singapore.

Additional collaboration continues in Nepal and further sample collections from primates and their environment are presently underway in Thailand.

“This type of MRSA is found all over the world and is a pandemic strain,” said Roberts. “The importance should be stressed in respect to these populations of wild animals. Even feeding chipmunks or ducks human food is not a good thing. They can pick up what we have and we can pick up what they have.  Some of the infectious agents in wildlife carry can be deadly.” Dr. Roberts is hoping for further funding, so that we can do additional monitoring of wild primates.

Research from several institutions, including the Washington National Primate Research Center (WaNPRC) at the University of Washington, suggests that more women could be losing their pregnancies to the Zika virus (ZIKV) without knowing they are infected. The study, published in Nature Medicine on July 2, found that 26 percent of nonhuman primates infected with Zika during early stages of pregnancy experienced miscarriage or stillbirth even though the animals showed few signs of infection. Contributors to the study included the WaNPRC’s Dr. Charlotte Hotchkiss and Core Staff Scientist Dr. Michael Gale, Director of the Center for Innate Immunity and Immune Disease.

ZIKV-associated pregnancy loss may be underreported, but the adverse outcomes of sensory defects and fetal brain malformations are well-documented. Children exposed to the Zika virus either in pregnancy or early in life should also be monitored into adolescence for signs of subtle neurological damage — even if they appeared normal at birth, say researchers at the University of Washington School of Medicine and their colleagues in an editorial published in June in the scientific journal Trends in Microbiology.

“Although we haven’t heard much about Zika in the last year, the virus is still circulating in the Caribbean, Central and South America, Southeast Asia and Africa – and it remains very dangerous to pregnant women and children,” said Dr. Kristina Adams Waldorf.

Adams Waldorf and co-author Dr. Lakshmi Rajagopal, a UW associate professor of pediatrics, wrote a paper is titled, “Congenital Zika virus infection as a silent pathology with loss of neurogenic output in the fetal brain” which was published in Nature Medicine in February of this year (2018).

Learn more at UW Medicine and PBS News Hour.

“We’re talking about the number one cause of death in the world [for humans],” said study author Dr. Charles Murry, director of the Institute for Stem Cell and Regenerative Medicine (ISCRM) at the University of Washington. And at the moment all of our treatments are … dancing around the root problem, which is that you don’t have enough muscle cells.”

After inducing heart attacks in macaques, the percent of blood their hearts pumped out with each beat dropped from roughly 70%, which is normal, to a weaker 40%. One month later, five monkeys who received human embryonic stem cells recouped 10.6 percentage points on average, versus only 2.5 in the control group. The paper titled, “Human embryonic stem cell–derived cardiomyocytes restore function in infarcted hearts of non-human primates” was published in Nature Biotechnology. Authors include WaNPRC’s Keith Vogel, Cliff Astley, Audrey Baldessari, and Jason Ogle.  Learn more at CNN and GeekWire.

Courtney joined the WaNPRC in March of 2018. She was brought on board during a transition within the Finance Division’s grant operations. This was also amidst Ann Schmidt’s retirement after her 36 years of service here. Courtney describes herself as highly motivated and goal oriented as a senior grant & contract management specialist. She has a Master’s degree and within her 17 years of experience has tested for and achieved credentials as a Certified Research Administrator and Certified Pre-Award Research Administrator.

She has a background clinical and biomedical research and administration within academic, for-profit, and non-profit settings. Her extensive expertise covers the entire grant life cycle with contract management, clinical site and research contracts, federal and non-profit grant applications, awards, subcontracts and sub awards.

Courtney is poised to expand our grant portfolio and increase research funding. These operations have obvious impacts upon all of us employed at the Primate Center.

Could you please briefly describe your role as Grant and Contract Manager?

I am involved in the pre-award phase of the grant application process which includes the non-scientific sections and the routing of the complete application to the Office of Sponsored Programs. I also work with outside investigators on the scope of work, coordinating with Jesse Day and the Finance team to assess that our facilities, resources and capabilities are compatible with their projects.

Have you held prior positions that will help you in your relatively new role here?

In my last position as Grants Manager at Swedish Health Services, I provided entire life-cycle grants management for all research units, from proposal development through closeout. I ensured the timely submission of the Research Performance Progress Reports for their various grants. I was also considered the “resident expert” in the funding agency’s requirements. After the merger of Swedish with Providence Health & Services, I was named to the Grants Management Team tasked with harmonizing a uniform grants management approach across both organizations.

Do you have a background in science?

My education includes a Master’s in Biology. Prior to pursuing work in grants management, I was enrolled in a Cellular and Molecular Biology doctoral program.  I have also worked in the private, biotechnology industry as an analytical chemist and nuclear magnetic resonance spectroscopy specialist.

It seems like that scientific experience would give you something in common with the PIs that you assist. What are the main challenges of your position?

My challenge is to make sure that the PIs here are informed about funding opportunities. I also would like them to be aware of the fact that I am here as a resource for the application process.

What are some of the business systems and interfaces you utilize in your position?

Let’s start with eRA Commons (Electronic Research Administration); the grants management portal at the National Institutes of Health. The NIH defines it as an online interface where signing officials, principal investigators, trainees and post-docs at institutions/organizations can access and share administrative information relating to research grants.

Their website offers this description:

eRA provides critical IT infrastructure to manage over $30 billion in research and non-research grants awarded annually by NIH and other grantor agencies in support of the collective mission of improving human health.   eRA systems, including eRA Commons, ASSIST and IMPAC II modules, support the full grants life cycle and are used by applicants and grantees worldwide as well as federal staff at the NIH, AHRQ, the CDC, FDA, SAMHSA, and VA.

The UW has SAGE – the System to Administer Grants Electronically. It interfaces with Grants.gov and allows you to submit funding applications for consideration, route them electronically for approval, request advance budget numbers, and initiate sub awards.

Do you have any closing thoughts?

I just want everyone to know that I look forward to taking a hands-on approach and I may be more involved in the grant process than Investigators here may be used to or early career PIs may even know about. The important takeaway is that I am happy to help beyond sending out FOAs (Funding Opportunity Announcements). Thanks for making this platform available to me to share with the Center.

Contact info for: Courtney A Miller, MS, CRA, CPRA

Grant and Contract Manager

OFFICE HOURS: 6 AM to 2 PM M-Th | TELEWORK: 6 AM to 2 PM F

MAIL: Box 357330 | OFFICE: 206.616.3812 | CELL: 205.317.8400 | EMAIL: cmiller6@uw.edu

When and how did you first arrive here at the UW and Primate Center? What was your path to the position you are now leaving?

I graduated as a Vet Tech (Pierce College) in 1979.  I was working at the old Emergency Vet Hospital with Bill Morton, who was also the WaNPRC Supervisory Vet at the time.  He ‘recruited’ me into the WaNPRC, as the overnight, graveyard vet tech, in 1982. So my first few years here were passing out meds, treating minor injuries, checking lixits and water filters, assisting feeding times at the Infant Lab, and “other duties as needed.”

After I moved to daytime working hours, I had the opportunity to work in many areas of the Primate Center – daily clinical support, tissue program, surgery, etc.  After being the Vet Tech assigned to the Infant Lab for some years in the late 80s/early 90s, I was offered the opportunity to work with the AIDS-related research projects.  This was early in the AIDS outbreak and it was the policy to limit the personnel with access to the animals assigned to those protocols.  So a small number of staff were responsible for the conduct of the experiments, data collection and the daily oversight of their clinical status. This was before the existence of the Research Support Services – actually, this small group became the ‘seed’ that the RSS sprouted from.  It became clear that having consistent research support from staff that were comfortable with the animals, liked the animals and were a familiar presence to the animals, was a benefit to both the study and to the animals’ well-being.

The outgrowth of the research work developed into helping PIs develop the budgets for their studies.  After a time, the hands-on animal work had to become a part of my past.  The budget developments became a full-time effort assisting PIs with their pre-award processes, for scientists within the Center, other UW departments, and other institutions.

Looking back on your years at the Center, what are some positive changes you have seen in NHP research? What possibly has stayed the same?

I think the thing that really stands out to me is the recognition of the need for the Psychological Well-Being (PWB) and the Environment Enrichment programs.  There had always been efforts made on the part of individuals.  Having a mandated program, with coordinated supervision, has been a pleasure to observe.  Even though I personally have not had any interactions with the animals in a number of years, I know the staff in the program are passionate about their work and the PWB of the animals is in good hands.

The hope is that we are constantly making things better, faster, smarter or less expensive. We try to strive to do more—with less. Perhaps tell us about a project or problem that you improved in these ways.

I’d like to think that I am a solution oriented type of person, with a eye out for areas that could benefit from changes (and coincidentally making my job easier).  Some of these improvements are still being used today, albeit with updates and modifications as warranted.  After all, every process, every form, every SOP should always be seen as a living thing with changes made as time, circumstances, rules and guidelines and technology move forward.  There is no improvement that can’t be improved.  I am proud that some of the seeds I have planted have shown value and have grown.

What’s next for you, Ann?

Disneyland?

A piece on Dr. Eberhard Fetz, WaNPRC core staff scientist and professor of physiology & biophysics has appeared within the cover article published in the January 4^th issue of The Economist. The piece, as part of the Technology Quarterly, focuses on the science of thoughts controlling machines.

“BCIs have deep roots. In the 18th century Luigi Galvani discovered the role of electricity in nerve activity when he found that applying voltage could cause a dead frog’s legs to twitch. In the 1920s Hans Berger used electroencephalography to record human brain waves. In the 1960s José Delgado theatrically used a brain implant to stop a charging bull in its tracks. One of the field’s father figures is still hard at work in the lab.

Eberhard Fetz was a post-doctoral researcher at the University of Washington in Seattle when he decided to test whether a monkey could control the needle of a meter using only its mind. A paper based on that research, published in 1969, showed that it could. Dr Fetz tracked down the movement of the needle to the firing rate of a single neuron in the monkey’s brain. The animal learned to control the activity of that single cell within two minutes, and was also able to switch to control a different neuron.” Read more at The Economist.

The strategy introduces stable components of flu virus to the body to spur universal, and long-lasting DNA-enhanced protection.

Getting a flu shot every year can be a pain. One UW Medicine researcher is hoping to make the yearly poke a thing of the past with the development of a universal vaccine that would protect from all strains of influenza virus, even as the viruses genetically shape-shift from year to year.

The research in Deborah Fuller’s lab uses a DNA vaccine to instruct the individual’s own skin cells to produce antigens and induce antibodies and T cell responses to fight the infection. Her most recent research on this effort was published today in PLOS ONE.

“Relatively speaking, DNA vaccination is the new kid on the block with regard to the types of vaccines,” said Fuller, a professor in the Department of Microbiology at the University of Washington School of Medicine. This year, U.S. medical professionals expect a challenging flu season, with 7,000 confirmed cases reported nationwide by the end of November – double the number from last year at the same time, according to the Centers for Disease Control and Prevention.

The DNA vaccine in Fuller’s lab was engineered by using genetic components of influenza virus – the conserved areas – which do not change. This is one way Fuller’s DNA vaccine gets around the genetic drift, or changes, that occur in influenza strains from year to year, and challenge clinicians who combat the disease.

It is also administered through the epidermis with a “gene gun” device that injects the DNA vaccine directly into the skin cells. The cells then produce the flu vaccine and prompts the body to create antibodies and T-cells to fight infection.

“With the immunized groups, we found that using this conserved component of the virus gave them 100 percent protection against a previous circulating influenza virus that didn’t match the vaccine,” Fuller said. “This was very exciting for us.”

The vaccine developed by Fuller’s lab takes a different approach to attacking the influenza virus within the body. Instead of simply repelling the virus, as on-the-market vaccines do now, this vaccine seeks out infected cells and kills them. The T-cell responses against the virus were so swift and complete in the tested non-human primates that they simply did not get sick, she said. Fuller’s team also was able to direct the T-cells to go to the lungs first, where much of the damage of an influenza infection occurs.

Another advantage: This approach requires production time of about three months, whereas it typically takes about nine months to produce the U.S.-approved vaccine for a flu season that begins in December (in the United States) and runs through February.

Fuller firmly believes this is the new direction of vaccine research.

“We’ve been working essentially with the same vaccine (techniques) over the last 40 years. It’s been a shake-and-bake vaccine: You produce the virus, you kill the virus, you inject it. Now it’s time for vaccines to go through an overhaul, and this includes the influenza vaccine.”

A “universal” vaccine would eliminate the need for yearly flu vaccinations and could be on-hand for rapid deployment should a deadly pandemic strain of the virus emerge.

The idea of a DNA-based vaccine might also pose a mechanism for vaccines for other viruses, such as Zika, and for possible pandemic outbreaks which might emerge in the future, she said.

But don’t expect the vaccine in Fuller’s lab to appear on the drugstore shelves anytime soon. It can take five to 10 years from the time a vaccine shows promising results in the lab to commercial availability.

A deeper look into this research:

In the Fuller lab, senior research scientist, Jim Fuller, engineered a vaccine that contained DNA coding for viral proteins from four different influenza A strains. These proteins, called HA, are targeted by standard vaccines and are known to trigger a strong immune response to each individual strain. In addition, the vaccine included DNA for a protein that is highly conserved and, thus, shared across different strains of virus.

Because DNA vaccines often fail to generate a strong immune response, the researchers sought to boost the vaccine’s effectiveness by fusing the DNA for some of the antigens with DNA proteins from a bacteria, a toxin from E. Coli, and protein from the hepatitis B virus that are known to be antigens that elicit a strong immune response.

In an animal study in cynomolgus macaques, researchers in the Fuller lab, Drs. Merika Treants Koday and Jolie Leonard, found that after three doses, the DNA vaccine generated a strong antibody response against each of the flu strains it targeted. Antibodies bind to and help clear microbial invaders, preventing an infection from taking hold or reducing its severity.

More importantly, the vaccine triggered a strong cellular immune response that was effective not only against the strains covered by the vaccine but also strains that were not.

Deborah Fuller was the co-inventor of the gene gun used in this research, and co-founded Orlance, Inc. a startup which is working on engineering a clinical version of the DNA vaccine delivery system and commercializing it for vaccines, including influenza.

This project has been funded by National Institutes of Health, National Institute of Allergy and Infectious Diseases (https://www.niaid.nih.gov) NIH/NIAID U01 AI074509 to DHF; NIH/NIAID, Department of Health and Human Services under Centers of Excellence in Influenza Research and Surveillance (CEIRS) (http://www.niaidceirs.org) contract HHSN272201400005C; and NIH/ORIP P51OD010425-51 to WaNPRC. The funders had no role in study design, data collection and analysis, decision to publish,or preparation of the manuscript.

UW Medicine writer Michael McCarthy contributed to this report.

Published on: Oct 6, 2017
The Washington National Primate Research Center was tapped to serve as the coordinating center to oversee the combined pledge of funds from the NPRCs in California, Georgia, Louisiana, Texas, Washington and Wisconsin totaling $30,000.

This aid will arrive in Puerto Rico by way of a container ship with vital supplies and equipment. The NIH is facilitating these operations, and FEMA is prioritizing urgent animal support supplies in order to avoid some of the supply chain backups that have plagued ground distribution in the aftermath of Hurricane Maria.

Noah Snyder-Mackler, assistant professor of psychology here at UW, is providing leadership to a diverse group of stakeholders including coordinating efforts with the NPRC consortium, the non-profit “Better Research, Better Life Foundation” (BRBLF), and investigators from New York University, University of Pennsylvania and the University of Exeter in England.

 

 

“It’s hard to fathom how these small monkeys managed to weather such a powerful storm, but they are not out of the woods yet,” said Snyder-Mackler. “We need to mobilize our resources to rebuild the infrastructure on the island as well as that of the community that supports it. If we don’t, we are at risk of losing one of our most valuable scientific resources.”

Two GoFundMe sites have been set up in conjunction with these operations: Cayo Santiago Monkeys: Maria Relief and Relief for Cayo Santiago Employees. An update from the latter page reads: “One NY-based colleague who will be flying to Puerto Rico on Tuesday with supplies for Cayo Santiago facilities (tools and a satellite phone that will greatly improve our ability to communicate with those in Punta Santiago) is also bringing some much needed relief for Cayo Santiago employees, including solar-powered USB chargers, solar flashlights, crank radios, batteries, water filtration systems, and formula and powdered milk for staff with young children.” This page has raised over $50,000 in donations to this point.
New York University assistant professor of biological anthropology James Higham discussed the hurricane’s impact and the relief efforts of academic institutions already underway.

 

Additional reading: “Study finds survivors of weather-related disasters may have accelerated aging”