Dr. Mark Hildebrand’s algae education program was top rated by the DOE’s Bioenergy Technologies Office Photo: Scripps Institution of Oceanography at UC San Diego

Dr. Mark Hildebrand’s algae education program was top rated by the DOE’s Bioenergy Technologies Office Photo: Scripps Institution of Oceanography at UC San Diego

by David Schwartz

Anew report issued by the U.S. Department of Energy’s Bioenergy Technologies Office (BETO) ranked 28 Algae Technology Area projects. Dr. Mark Hildebrand and his team at Scripps Institution of Oceanography at UC San Diego were ranked the highest for criteria that included technical progress, project relevance, and critical success factors. The report specifically cited the lab’s “outstanding research” in the genetic manipulation of algae to improve the yield of key growth components for biofuel production.

The BETO report noted that Hildebrand’s project “is a tantalizing example of the need for and potential of genetic engineering to strongly contribute to productivity increases,” and added that “algal feedstocks can provide high-yield renewable oils that are well suited to displacing petroleum-based fuels and products.”

“The main focus of our project,” says Hildebrand, “was to demonstrate the feasibility of using genetic manipulation approaches for metabolic engineering. And the system we worked on was very amenable to doing that. Some diatoms are very easy to manipulate, especially relative to the green algae, where it’s more difficult to manipulate nuclear genes, and I think that’s what the big difference was. We were able to apply the technology quickly into an amenable system.”

Dr. Hildebrand, a Scripps research professor in the Marine Biology Research Division, received his Ph.D. in biochemistry from the University of Arizona, and did his post-doctoral work with Benjamin Volcani at Scripps Institution of Oceanography. He has been involved with algae research for 26 years, and with biofuels specifically for nearly eight years.

“Scripps has a unique perspective in being able to apply long-standing interests in algae productivity in the oceans to the technological application of algal productivity for biofuels,” said Dr. Hildebrand. “These high rankings indicate that Scripps and UC San Diego are among the best institutions for algal biofuels research in the world. This relates not only to the quality of the science, but to the training of students, as evidenced by recent pioneering publications led by Ph.D. student first authors. We are training scientists and policy makers who will shape the future development of renewable fuels.”

AIM recently spoke with Dr. Hildebrand to find out more about his lab and the award winning research being done there.

What first interested you in algae research?

I came to Scripps to do a post doc. I was a plant biochemist as a graduate student and at the time there was a professor at Scripps who was doing the only cutting edge molecular biology on diatoms. These organisms, in addition to being highly productive in terms of their photosynthetic capability, make cell walls out of silica – basically glass cell walls in very intricate and ornate shapes. And so my initial interest was to work on them to develop general molecular biology tools. Then I got really fascinated by the silica structure side of things. For many years that was our major project in the lab – how diatoms make their silica cell walls.

About seven years ago I got a call from Eric Jarvis at NREL saying that the Air Force had started up an algae biofuels program, and he asked if I wanted to participate. I was interested in that because a lot of the tools we were developing for other work applied also to biofuels, so we got immersed through that route.

What was the purpose of the research work that was just recognized by the DOE?

The purpose was to demonstrate that you could do metabolic engineering to improve lipid content without negatively affecting growth. We did three different manipulations that accomplished that goal. One has been published and we have two others that we are wrapping up.

So in your lab today, what major projects are getting the most attention?

There are three major ones. The biofuels project still has a lot of work to be done. We have other projects where we’re looking at how diatoms make their silica cell walls, and that involves also doing genetic manipulation to change their structure. There are potential nanotechnology applications involved in that. The third major area we’re working on is therapeutic protein expression in diatoms. The idea there is to express proteins at high levels in these organisms, and then use them as vaccines.

In terms of the biofuels work, we’re continuing to do fundamental manipulations in the lab, but we’d like to start to test these things out under authentic production conditions. That means growing under light/dark cycles, interacting with people who are doing production, and testing out how the modifications are going to stand up in the real world. We’ve always been rooted in that concept, even when we do our manipulations in the lab. It’s always thinking about: could this be useful in a production system?

Some of your students are beginning to make names for themselves through their work at your lab. Can you give us an example of students contributing to the knowledge base of the industry?

Dr. Emily Trentacoste is currently on a fellowship to change the policy in D.C. about algae for biofuels.

Dr. Emily Trentacoste is currently on a fellowship to change the policy in D.C. about algae for biofuels.

One student in particular, Emily Trentacoste, who published a paper in PNAS last year, which was our first published demonstration that we can increase lipid levels without affecting growth negatively. She just completed her PhD and she’s currently doing a policy fellowship in D.C. Her longer-term interest was to get into policy, and so she can translate her researched-based training into changing the policy in D.C. about algae for biofuels.

Five years ago there was a lot of attention on algae for biofuels. And as time has passed things have diversified, with a lot more attention right now on health and medical applications. How do you see this changing, say, over the next five years? Where will the opportunities be for future graduates of algae programs?

The fundamental thing is that you can look at algae as a highly productive platform – they grow very well with very little nutrient input. They’re inexpensive to grow, and you can adapt them to various applications. The fuels are one thing, but we also have projects looking at omega-3 production, and therapeutic protein expression, for example.

I think that all of the applications have potential to pan out, because the platform is amenable. Algae are so productive and, at scale, can reduce the cost of anything you want. These other products tie in with biofuel. After oil extraction, you can use the protein – or a specific protein — for some other purpose. I think it’s going to become very broad.

What motivates you to do this work?

There are several layers to it. The science is really interesting, and what I find fascinating about it is that we are looking at fundamental metabolic processes in algae cells that people assumed we understood based on more extensive work done in mammalian systems. But we’re finding out that diatoms in particular – their metabolic organization and the components they have in the cell – are really unique in nature. They have glycolysis in the mitochondria. They have a urea cycle, which is found elsewhere only in multicellular organisms. They’re fascinating at the metabolic level to unravel.

There’s also an interactive part to it. I really enjoy the stimulation I get from discussions with my colleagues and my students about the topic, because of a high level of interest and passion. It’s a new area, so everyone’s ideas are under consideration, and it’s just very stimulating.

We focus on a class of algae that is fundamentally different from green algae. We’ve been promoting the concept of the vast differences between different classes of algae because, metabolically, they are completely different from each other. People often make generalizations when they work on one species that these are what algae do. Quite frankly that is not even close to being accurate.

So we’ve been pushing the idea in some of our publications, and trying to collaborate with people where we examine different classes of algae. Ultimately if you want to work on a system that’s highly productive you have to appreciate that in the environment, you need to look at the different classes of algae to get a broad spectrum of what nature is capable of doing.

If you were to survey the natural environment for what are the most productive class of algae, diatoms are good candidates for biofuel production, and in the marine environment there’s no question about it. Diatoms are far and away the most productive eukaryotic algae in the oceans.

Scripps Institution of Oceanography Pier

Scripps Institution of Oceanography Pier

What are you most encouraged about as you watch this industry develop?

That most of the work that has been done in the past few years, even with the extent of funding available, shows that the technology is moving in the right direction at a fast pace. I’m convinced that the technology will work in a cost competitive way. We just need to pay attention to the problems and apply rational approaches and it will work out.

What frustrates you?

As with many PIs, I spend a lot of time writing grant proposals and in addition to the difficulties in getting projects funded, the relatively short-term nature of most grants does not translate into reasonable ways of supporting labs long term.

I would think that what would be valuable for funding agencies, if they’re going to rank projects, is to realize that investing in continuation of the top scoring projects makes sense for both the investigator and agency. There’s no mechanism for that right now, and our lab is struggling to get funding again, because that project is completed.

I think there’s a dichotomy between the practical realities of running a productive lab, where you’ve built up expertise because of the great people you have, and the shorter-term funding cycles. You need to keep the momentum continuously going if you’ve got a productive group. You’ve got to keep supporting it, because you’re only going to get more out of it.

I wasn’t shy about stating that our research should be continued, because we’ve just only demonstrated the first principles. We have the right team to do more, and it would be a good investment.

If you really want to make algal biofuels technology develop, a mechanism for continuation of good projects has to be put into the program.

Similarly, do you see a better way for industry to help fund research institutions for mutually compatible goals?

If projects of mutual interests can be developed, then yes, industry support is a good thing. We were supported by General Atomics on their DARPA-funded biofuels project and it work out very well, we gained insight into production issues related to algal biofuels, and we were able to deliver improved strains to GA, which substantially reduced the cost of production.

Dr. Hildebrand has been involved with algae research for 26 years

Dr. Hildebrand has been involved with algae research for 26 years. Photo: ©2014 Scripps Institution of Oceanography

Seems like there is redundancy in the research between industry labs vs. situations like yours, where more R&D could be outsourced instead of reinventing.

At times that’s true. Of course there are intellectual property issues that are important to companies, but usually those agreements can be worked out with the universities. Most companies are focused on developing production systems as quickly as possible, so they actually don’t have time to do research, and that’s where we could contribute substantially.

I think that would be an ideal situation, where we have a blend of academia and industry, in which observations that a company cannot follow up on becomes the focus of academic research, with an understanding that substantial improvements on the short term are still desired.

There’s a practical difference; we’re supposed to be exploring things, and a company is supposed to be getting a product out. So very often companies aren’t able to focus on what might be considered longer-term improvements, but ultimately those are the ones that pay off.

Is that something you see will eventually come together, or is there an intrinsic separation?

I hope it will. In some cases there is a difference in philosophy and often times companies feel that they have the expertise they need and they don’t want to open it up to someone else. I think right now the field is so young and our understanding is so much at the beginning stages that it would be of much more benefit if industry would share information more.

Sitting on the sidelines and watching it you realize that nobody really has all the answers. And there really aren’t any secrets. We’re all smart people and we’ll think of things that will work, and I think a little more sharing of information would make a lot of sense.