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Malaria parasite drug target

Candidate—Ellen Yeh, UCSF

Nominated by Joe DeRisi, UCSF

The Deloitte QB3 Award for Innovation recognizes a graduate student, postdoc, staff scientist, or team from UC Berkeley, UC Santa Cruz, or UCSF who has made an advance with the capacity to improve human health. Candidates for were nominated by QB3 faculty. Finalists were chosen by a panel of expert judges.

We asked each nominee (or team) to answer a series of short questions, to give a snapshot of their project. Read their answers below. Leave a comment to let us know what you think!


Ellen Yeh, MD, PhD. Photo: Jason Bardi, UCSF Public Affairs

Please describe your innovation.
Malaria-causing Plasmodium spp parasites contain an essential plastid organelle, the apicoplast, which is a key target for the development of anti-malarials. However, nearly 20 years after its discovery, the essential functions of the apicoplast remain a mystery. We use a simple chemical method to generate parasites that have lost their apicoplast, normally a deadly event, but which are “rescued” by the addition of a single essential metabolite. These apicoplast-minus parasites demonstrate that, surprisingly, the apicoplast has only one essential function during blood-stage infection, namely isoprenoid precursor biosynthesis. This finding has important implications and utility for therapeutic development.

Within the 140-character Twitter limit:

What’s the impact?
With 300 million cases and 1 million deaths per year, #malaria disproportionately affects the world’s poorest and youngest,

What’s the novelty?
We got freaky parasites missing an essential organelle, “rescued” by +ing just 1 metabolite! 20yof ?s —>wacky biology, life-saving therapy

What’s the utility?
Instantly defines druggable pathways AND easy specific drug screen. Ready to test as attenuated vaccine which improves on what’s available


In the malaria parasite, the ‘apicoplast’ normally segregates certain metabolites (left). Knocking out the apicoplast (right) removes the ability to segregate, and kills the parasite—because its survival depends on a single chemical produced by the apicoplast.

How does your research topic represent a strong advance in human health? And how will it influence the way we operate in science in the future?
Malaria is a profound human health problem that has shaped our evolutionary past and continues to influence modern day with a disease burden that disproportionately affects the world’s poorest and youngest. New anti-malarials are desperately needed in the face of existing or emerging drug resistance to all available therapies, while an effective vaccine remains elusive. Apicoplast-minus parasites define the essential pathway in the apicoplast and provide a pathway-specific screen to immediately begin identifying drugs that specifically target this essential function. Moreover, apicoplast-minus parasites are a potential attenuated vaccine strain with significant advantages over current vaccine technologies.

Reference:
Chemical Rescue of Malaria Parasites Lacking an Apicoplast Defines Organelle Function in Blood-Stage Plasmodium falciparum
Ellen Yeh and Joseph L. DeRisi
PLoS Biol 9(8): e1001138. doi:10.1371/journal.pbio.1001138

Magnetic Particle Imaging

Candidate—Patrick Goodwill, UC Berkeley

Nominated by Steven Conolly, UC Berkeley

The Deloitte QB3 Award for Innovation recognizes a graduate student, postdoc, staff scientist, or team from UC Berkeley, UC Santa Cruz, or UCSF who has made an advance with the capacity to improve human health. Candidates for were nominated by QB3 faculty. Finalists were chosen by a panel of expert judges.

We asked each nominee (or team) to answer a series of short questions, to give a snapshot of their project. Read their answers below. Leave a comment to let us know what you think!


Patrick Goodwill.

Please describe your innovation.
I developed the theory and scanners for X-space Magnetic Particle Imaging (MPI), a new medical imaging technique that will revolutionize diagnostic imaging. X-space MPI will enable real-time angiography without radiation or iodine, as well as cancer detection using dynamic contrast enhancement. X-space MPI theory describes how a combination of strong magnetic field gradients and time varying magnetic fields can produce an image of the concentration of an iron oxide tracer in the body. The theory has been the foundation for my construction of three generations of X-space MPI scanners, the latest of which recently acquired our first animal images.

Within the 140-character Twitter limit:

What’s the impact?
MPI enables radiation-free, iodine-free, non-invasive assessment of cardiovascular health, the leading cause of death in the US

What’s the novelty?
MPI is the first whole-body imaging tech to see a radiation-free tracer w/ perfect contrast, giving doctors a powerful new diagnostic tool

What’s the utility?
MPI has a clear path to the clinic. My latest (of three) MPI scanners can image rats, and I am now beginning to plan a human scanner


The latest version of the scanner, with a mouse loaded for imaging.

How does your research topic represent a strong advance in human health? And how will it influence the way we operate in science in the future?
Heart disease is the leading cause of death in the US. MPI will save lives by giving doctors a way to assess cardiovascular health in real-time without the dangers of radiation and Iodine inherent to the clinically dominant X-ray techniques. MPI will also give scientists and health professionals a way to non-invasively study the body. MPI sees only an iron-oxide tracer and does not see tissue, and so MPI contrast is comparable to nuclear imaging. Therefore MPI could prove a radiation-free means to track tagged cells such as stem cells homing to an injury or monocytes seeking out an infection.

References:
Narrowband Magnetic Particle Imaging
Patrick W. Goodwill, Greig C. Scott, Pascal P. Stang, and Steven M. Conolly
IEEE Transactions on Medical Imaging, Vol. 28, No. 8, August 2009

The X-Space Formulation of the Magnetic Particle Imaging Process—1-D Signal, Resolution, Bandwidth, SNR, SAR, and Magnetostimulation
Patrick W. Goodwill and Steven M. Conolly
IEEE Transactions on Medical Imaging, Vol. 29, No. 11, November 2010

Taiwanese electronics industry seeking bio interface


On my left, Wen-Tsuen Chen, professor, National Tsing Hua university, and program director of the National Program for Intelligent Electronics; on my right, Liang-Gee Chen, professor, National Taiwan University, and deputy program director of NPIE.

Although we often host visitors who don’t have backgrounds in bioscience, it’s rare for us to see a group all of whom are specialists in a non-life science field. But this afternoon I had the pleasure of giving a talk and tour to a delegation from Taiwan’s National Program for Intelligent Electronics: about twelve academic experts in electrical engineering and computer science.

What did they want from QB3? In email exchanges, it came out that they were looking for ways in which Taiwanese universities could collaborate with US universities in areas such as biomolecule detection (such as NMR spectroscopy) and nanofabrication for medical applications. So it was a good thing that I was able to get some postdocs and grad students from Tejal Desai’s group to talk about what they’re up to—various ways to use nanofabricated materials to create implants that release drugs slowly inside the body, in hard-to-reach places.

The visitors were also interested in QB3’s entrepreneur support and our incubators. They told me that at least two Taiwanese universities—National Tsing Hua University and National Taiwan University—run on-campus incubators that host about 30 companies apiece in a range of markets. They mentor their entrepreneurs, make seed stage investments (along the lines of our Mission Bay Capital) and when their startups graduate, at least at Tsing Hua, they move next door to a large science park, thus keeping the economic growth in the neighborhood. That’s something QB3 is designed to do at Mission Bay, although the science park at the moment is called South San Francisco!

One thing they were curious about was whether QB3 takes an equity stake in our incubator startups. They were surprised that currently we do not, for a number of reasons including our nonprofit status and the long payback time in life sciences. But enough people bring the topic up that perhaps we should consider ways to develop our incubators as a resource beyond rent-paying tenants.

Utah's prefab approach to startups

A prefab approach to startups is working for the University of Utah.


Jack Brittain let a QB3 audience in on the secret of how he does more with less at Utah.

Jack Brittain gave his long-awaited Innovation Policy talk today on what he’s doing at Utah to make it #1 in the country for the number of startup companies spun off per year. (That number is not normalized by size or funding.) Brittain is vice-president for technology venture development at Utah. A lot of people showed up—175 registered, and the room was pretty full, which I was pleased with and also a bit surprised by, because I hadn’t thought so many would be interested in policy. You can always count on students to show up for a free lunch, but the crowd was a good mix of students, postdocs, profs, Garage entrepreneurs, tech transfer folks, and Mission Bay industry.

You can download Brittain’s slide deck here.

Two aspects stood out in his talk, to me. The first was his emphasis on “fail fast, fail cheap.” His examples highlighted how expensive biotech is compared with tech and engineering in general. Utah emphasizes prototyping, and the university offers grants on the order of a few thousand dollars as long as startups can provide milestones to be met within a few months. That contrasts with startups in the QB3 Garage system, which all strive to win SBIRs in the $100k-$1M range just to operate for a couple years, because you can’t count on bio experiments to work within a few months.

“You should be able to make your prototype from stuff you buy at Ace Hardware,” Brittain said—which wouldn’t have worked for Amyris, though—and he had brought an illustrative example: a pill-sized plastic device to disinfect catheters in hospitals. Apparently catheter infections are a big deal and this is an unmet medical need. Two nurses had an idea for a gizmo to coat the catheter surfaces with disinfecting alcohol (these were male nurses, who rode Harleys and ran their own machine shop; they first tried a disinfection technique that involved vigorous open flames). Their first prototype was built from two toothpaste caps. It came a long way; the sophisticated-looking samples Brittain handed out involved more than 20 patents.

The second aspect was how Utah had focused on prototyping, commercial launch, and early market expansion. Brittain’s office offers, among other things, basic incorporation, logo and website creation (some people will spend months designing a logo, when they ought to be working on their product), market research, and insurance. This last seemed key to me, and Brittain made a point of it: young companies often hire much older technical advisors, who need health insurance much more than young people do. They are not going to sign on to a startup if it means dropping health coverage that it may have taken a lot of effort to qualify for.

It occurred to me that “fail fast” doesn’t work as a motivating slogan for such people, but perhaps if they can transfer to a different startup under the same health insurance program, it’s less of a problem.

Brittain included a slide with some impressive numbers cataloguing Utah’s startup pipeline: 72 companies are at the long-term growth stage, adding more than 6,000 jobs. In a state the size of Utah (2.5 million residents) Brittain’s program, which he has developed in only five or six years, has become a major economic engine.

QB3’s next Innovation Policy event will be a lecture by Congresswoman Jackie Speier on September 27.

Incubator launch a draw for government, business in Berkeley


Reg Kelly addresses government and business leaders at the incubator launch in west Berkeley.

Although QB3 is well-integrated with the mayor’s office and various economic development groups in San Francisco (for example, see our new BioSF initiative) we don’t often rub shoulders with government in the East Bay. Yesterday was different. Our real estate partner, Wareham Development, held a lunch launch for the new QB3 East Bay Innovation Center, a 10-15 company life sciences incubator in west Berkeley, close to either Novartis Diagnostics or Berkeley Bowl, depending on your priorities.

At the lunch (at Riva Cucina, a fine Italian place) a number of East Bay leaders spoke, MC’d by Chris Barlow, a partner at Wareham and the prime mover for the incubator. Congresswoman Barbara Lee cited the need for supporting diversity among scientific innovators; State Assemblymember Nancy Skinner argued for continued state support of early-stage companies that can translate university research into cures and solutions to transform society. Also addressing the group were QB3’s Reg Kelly and Wareham president Rich Robbins, who, according to Barlow, “needs no introduction…and therefore he won’t get one.” He didn’t.


Wareham’s Chris Barlow gives a tour of the incubator facilities.

Wareham is launching the incubator as part of a larger strategy in the life sciences market. They will provide space and services for young companies, and then turf them out after an incubation stage of a year or so. We do that too. But unlike the QB3 Garage, which focuses entirely on incubation, Wareham—they are a real estate company after all—can funnel the new companies from their incubator, which is just short of 10,000 square feet, into larger spaces elsewhere in the Bay Area.

The SF Business Times reported last week that Wareham was constructing a 94,000 square foot building (that’s the same size as Byers Hall, the QB3 digs at UCSF Mission Bay) in Emeryville, destined for life science companies. Vacancy in this market is very tight—1% apparently. That’s worse than apartment rentals in Berkeley!

The QB3-EBIC incubator is at 2929 Seventh Street, an address putting it in the middle of an emerging greentech/cleantech corridor between Berkeley and Emeryville. The opinion of many people I spoke to was that the momentum of development was unstoppable; entrepreneurs coming out of UC Berkeley needed space to turn their ideas into companies, and the city leadership was determined to keep the entrepreneurs close to home rather than letting them escape down to Silicon Valley or off to San Diego or Cambridge, MA as they had in the past.

Read today’s story about the QB3-EBIC in the Contra Costa Times

Thinking outside the country


But do they speak jargon? Europe-posted US diplomats visited QB3 on May 10.

With our focus on the California economy and research at UC, we don’t think too much about working with groups or institutions elsewhere in the US, let alone across the world. Of course we like to learn what we can about the challenges that organizations like QB3 face, and how they are meeting them. And our Global Bio-Entrepreneurship course has to date been funded by the Malaysian government. But when it comes to real collaboration, real money and real working hours, we have enough on our hands just connecting people at Berkeley, UCSF, and Santa Cruz.

Which is why it was a mind-expanding experience yesterday when we hosted a group of eight US diplomats serving in Europe. They were in town for an annual meeting and had, earlier in the day, visited a couple IT companies; now they were at QB3 to learn about biotech.

They have very impressive resumes, these people. Stephen Anderson, for example—commercial counselor at the US embassy in Dublin, Ireland. He’s fluent in Chinese and Japanese and has served in China and Japan. (One wonders: Gaelic, too?) Oh, and he also has a PhD from MIT.

Anderson gave me a handout summarizing the Irish biotech sector. Life sciences in Ireland employ 40,000 and generated $46 billion in exports last year. It was hard for me to get a handle on this, but among the countries to which the diplomats were posted, Ireland (and Sweden, and Spain) seemed to be leaders; other countries, such as Romania, were not nearly so far along. Romania is apparently a place that global companies go to conduct clinical trials.

One official told me that the attitude of a country’s population is a big factor in whether sophisticated industrial science will succeed. “You need certain basic functions,” he said, “like respect for the rule of law.” In a certain post-Soviet country, he said, “if I manage to cheat you, that’s not wrong; it just means I’m more clever than you.” Imagine how this country would regulate drug discovery.

When I asked what they were interested in, the officials said they wanted to know how QB3 was working with companies in other countries. (D’Oh! That’s what I get for asking someone in the Foreign Service.) I mentioned that, in the QB3 incubator system, we have at least three “lily pad” companies that want a tiny footprint in the Bay Area to get access to venture capital in Silicon Valley. I also said that the local biofuels industry, captained by Jay Keasling’s Amyris, has developed a strong link to Brazil and its sugarcane/biofuel sector.

Would QB3 get anything worthwhile out of collaborating with a group in another country? It depends. It depends on who’s involved on both sides, and what we and they stand to gain. The details are what matter, and this also holds for trade diplomacy. One official said that whenever he considers how the US might participate in the local economy, saying the partnership will be in “biotech” isn’t good enough. He has to know exactly which sector, which companies, which personalities. Otherwise it’s money and time wasted.

Now that's an incubator


Tourists: Dan Mogren and Evy Lundgren-Akerlund can’t resist taking a photo of Refactored Materials’s golden orb weaver—currently the sole tenant of the spider farm.

Two Swedish visitors dropped in last Thursday to see the Garage@UCSF, and left us with a new perspective on the scale and goals for a life sciences incubator.

Evy Lundgren-Akerlund, a professor and CEO of the Lund Life Science Incubator, and Dan Mogren, the incubator’s manager of business development, had seen Bio-X at Stanford and the San Jose BioCenter earlier in the day. (After QB3, they flew to Stockholm on United, an ordeal made all the more cruel because they had thought they’d be on Lufthansa.)

Mogren explained that the two were on a knowledge-gathering trip because they had a big development project back home. Astra-Zeneca has moved out of a 1 million square foot facility in Lund—a city in southern Sweden not far from Copenhagen—and the Life Science Incubator, which currently occupies space on the order of 20,000 square feet, was doubling in size. “To become a normal-sized incubator,” Mogren said.

I mentioned that the Garage@UCSF takes up 2,500 square feet, and Mogren quickly added that of course quality is important.

Lundgren-Akerlund and Mogren told me that a major goal of their incubator is to prepare young companies so they can move away from Sweden, or set up branch labs/offices, in key markets such as California. This is completely different from our mandate to nurture companies so they can forge connections locally and take root in the region. But, for example, Sony Ericsson has been very successful globally. I’m not sure how foreign success would feed back to Sweden.

Mogren was particularly interested in how QB3 planned to grow our incubator system, which at present consists of the Garage@UCSF, the Garage@Berkeley, and the Mission Bay Innovation Center at FibroGen. I said that it was near-impossible for us to expand the space on campus because of the restrictions on commercial usage at a public university. The future for QB3 in this dimension is to partner with private companies that have free space, and in particular with real estate companies that have whole buildings at their disposal. See, for example, our partnership with Wareham to launch an 11,000 square foot facility in South Berkeley. The trick will be to extend our warm family feeling to startups in these “satellite” (but much larger) incubators.

That bench is ours


Nick Toriello as roadie: moving the contents of Allopartis’s -80 C freezer across 3rd St.

Ever since I started working here, I could count on someone from Allopartis being up for a chat about life, hockey, or molecular biology. Two of the founders—Nick and Charlie—are friends of mine from grad school at UC Berkeley, and I’d gotten to know Robert, Rich, and Nitzan well. They’d certainly had ample opportunity to get tired of me, as I led yet another tour through the Garage or hounded them to participate in yet another photo or video shoot. But Allopartis grew up, and now they’re gone, across 3rd St. to the Innovation Center at FibroGen.

This gives me an excuse finally to go over there. I’m always telling visitors about FibroGen but I’ve never seen the space for myself.

Allopartis, which uses directed evolution to develop enzymes to digest cellulose into sugars for biofuel production, rented space in the Garage for over 2.5 years. The usual ceiling for Garage companies is 2 years, but we’re flexible. Especially if people are happy to talk to reporters and smile for photographers. Allopartis grew slightly too fast for its own good, and with 5 people on payroll, had to work hard to secure enough funding, even though they landed a $1 million federal SBIR grant last year. But they were successful in the end.

Into the vacuum left by Allopartis—the entire central bay of the Garage@UCSF—the other companies expanded like overstuffed packing peanuts. I was just in there, and Omniox has taken over one side, while Lypro has most of the other. Lypro hasn’t got boots on the ground yet; they’ve claimed the space with handwritten notes.


High-tech real estate management system.

Lypro and Omniox didn’t get it all, though. One tiny bench, 100 square feet (the minimum we rent) has been reserved for a new UCSF startup that I’m not able to talk about yet.

Omniox has hired a new protein engineer, Feng Yen. At first I thought Feng was the co-founder of the new company, but he soon cleared matters up for me. Feng is employee #7 at Omniox. Seven employees at a Garage startup! And what’s more surprising is that I often see most of them in there at the same time, scattered around the area. I hadn’t realized Omniox had grown so big. They’ll definitely be looking for new premises.

Venture capital in the house


Eric Springman (left) and Michael Hanley (right) of Celtaxsys. Reg Kelly was Michael’s PhD supervisor.

Reg had a blast from the past yesterday: Michael Henley came by the office. Reg was Michael’s PhD thesis supervisor many lives ago. Since that time, whenever it was, Michael has worked at the MRC lab at Cambridge (at the same time as Watson and Crick); served as a professor and won tenure at UC Davis; and entered and left private industry a few times. Right now he’s CEO of Celtaxsys, a young company that is developing a biochemical cell-repellant as a medical therapy applicable to many diseases.

Chemoattraction is a well-known phenomenon in molecular biology: cells, for example in the immune system, secrete chemicals that recruit other cells to perform tasks like fighting a local infection. But once the infection is vanquished, where do the cells go? Some of them undergo a programmed shutdown. Others are instructed, via chemorepulsion, to make themselves useful elsewhere. That’s what Celtaxsys is focusing on.

Celtaxsys was founded in Atlanta, and that’s where their wet lab is, but they now have an office at Mission Bay, at 1700 Owens St. Michael enthused about the location. He’d briefly considered South San Francisco because it was cheaper, but, he says, the density of connections to be made at Mission Bay made it much more attractive.


The new Sand Hill Road? Enjoy the classy lobby with free iMac use and internet access.

In particular, 1700 Owens St. hosts a number of representatives of major venture capital firms. It’s practically a new Sand Hill Road, Michael says, “and it came up by stealth.” In fact, so stealthily that I don’t know much about it myself—I took a walk over there to get an image for this post. (I’d show you the plush interior, but the security guard forbade me to photograph.)

There are two VC offices on the same floor as Celtaxsys. For a startup or early stage company seeking investors, there is no better place to be. Even if your pitches fail at first, you don’t have to go far to practice!

I am not sure exactly which firms are in there. There is no list in the lobby. Our standard Powerpoint presentation on Mission Bay, created by Doug Crawford, mentions Arch Ventures, Column Group, Novo Ventures, Synergenics, and
Versant Ventures.

Entrepreneurial ideas from Seattle


Chris Igielski was as keen to take photos as we were.

It was a real pleasure today to welcome two visitors from the University of Washington’s Center for Commercialization: industry relations officers Chris Igielski and Terry Grant. Doug was the man they had come to see, of course—he’d given a keynote address at a symposium they held last year—but while we waited for Doug, we had an enthusiastic exchange of ideas around incubators, tech transfer, and entrepreneurship in general.

Chris and Terry are in the Bay Area for an economic tour of San Jose and Silicon Valley on behalf of four counties in Washington State. They’re hoping to learn some lessons that they can apply back home. They told me that they were particularly interested in the QB3 Garage because UW doesn’t have an on-campus incubator.

Terry previously served as an entrepreneur-in-residence at UWC4C. (He’s got a PhD in chemical engineering from UC Berkeley and much experience in industry.) The reason that QB3 also has entrepreneurs-in-residence is that Doug was inspired by his visit to UWC4C. We now have three EiRs; they list nine as their “newest” arrivals.


Terry Grant.

Terry says that EiRs play a vital role at centers for commercialization, because they smooth the path for VCs to invest in startups. According to Terry, VCs don’t pay too much attention to a startup’s technology or market share or the details of the business plan. They want to hear the “story,” and they look closely at the person who is telling it. If they trust that person—if he or she is confident and delivers a strong pitch, and has a record of successful startups—they believe that he or she is in control, and can take care of the details.

I’d take that to mean that for every EiR a center for commercialization hires, at least one startup will make it to the first round of venture financing.

Terry was a bit surprised that we don’t pay our EiRs, but agreed that EiRs in general are already financially secure and are playing the game for its own sake.

I asked Chris whether he thought there was anything QB3 could do to improve. He said that we might benefit from having a full-time grant writer (or fraction thereof) supporting our startups as they apply for SBIR grants.

We hope to see Chris and Terry again and to keep in contact. We’re impressed with what UWC4C and Washington are doing to harvest and nurture innovation in-state.

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