Algal Biotechnology in the Gerwick Lab: From Pharmacy to Fuel

By R. Cameron Coates

 

Drs. Bill and Lena Gerwick

Dr. Bill and Dr. Lena Gerwick lead the Gerwick lab and have developed an effective style that builds on their respective strengths in chemistry, molecular biology, innate immunity and microbiology.  Bill describes himself as “incredibly lucky” to be working with Lena everyday, because despite the complexities it can sometimes create, they “get the chance to interact on such a multi-dimensional way.”  It is, however, the interdisciplinary nature of the Gerwick lab as a whole that makes them a unique group of scientists.  Dr. Bill Gerwick sees the lab’s interdisciplinary qualities as valuable because “it is at the confluence of a variety of disciplines where one finds a rich interface that is ripe with opportunity and innovation.  We consciously try to create that interface in the context of a lab through the basic application of biology, analytical and organic chemistry, pharmaceutical sciences, molecular biology and biosynthesis.” By bringing together an expertise in these varied disciplines the lab has been able to explore the unique chemical adaptation of marine algae and cyanobacteria and how those adaptations might be useful in a variety of biomedical or biotechnological applications.

To explore the unique chemical adaptations of marine life one needs to travel to unique habitats.   Dr. Bill Gerwick and his students make regular collection trips to distant locations to find novel strains of algae and cyanobacteria.  “Each collection trip takes us to new parts of the world at different times of the year and we find different organisms.  Those organisms are the engine that drives the downstream chemistry and biology pursuits of our lab.” The lab has accumulated samples from 16 different countries including remote places like Papua New Guinea, Panama, Madagascar and even Palmyra Atoll in the middle of the Pacific.  From these trips Gerwick and his students bring back live samples as well as larger collections preserved for chemical investigations and DNA isolation.  It is from this treasure trove of samples that the lab has amassed a collection of over 100 live cyanobacterial strains in culture, over 18,000 extracts and purified fractions and 129 pure compounds.  Maintaining a culture collection of so many strains is no small task and Tara Byrum (a multi-talented biologist/lab manager) is the one who keeps it all running.  “It’s exciting to see all of the samples coming into the lab from collection trips and having seen what happens with the samples afterwards I really like how we use chemistry and molecular biology for such a multi-disciplinary approach “

Dr. Bill Gerwick and the author, graduate student Cameron Coates, on a collection trip in Papua New Guinea

            The isolation and identification of natural products from marine algae and cyanobacteria has been a major focus of the lab over the last 25 years.  This effort has yielded compounds like Curacin A, an anti-cancer drug candidate that is active against colon, kidney and breast cancer cell lines.   The compound was isolated from a filamentous marine cyanobacterium from Curacao in the late 90’s and the unique structural characteristics and activity it possesses has driven the lab to investigate the biosynthesis of this molecule and learn more about its activity against cancer cells.  Moorea producta, the cyanobacterium that produces Curacin A, also produces a variety of other novel secondary metabolites.  The lab recently sequenced the genome of this cyanobacterium to investigate the pathways involved in producing Curacin A and these other secondary metabolites.  The results of this sequencing project were recently published in PNAS and can be found here.

Lab Technician Tara Byrum

            The lab plans to maintain their effort in drug discovery while joining forces with SD-CAB and applying their expertise in organic chemistry and molecular biology to biofuel applications.  Growing interest in developing algae as a source of biofuels has opened up many opportunities for the lab to explore new projects that connect their work in natural products to biofuels.  For example, the biomass that remains after the algae has been extracted for fuels may contain compounds that could be used for other biotechnology applications like a pharmaceutical.  These compounds are commonly referred to as “co-products” and members of the Gerwick lab are actively working on identifying potential co-products.   Separately, the lab is working more directly on biofuel applications using cyanobacteria and diatoms.  Emily Trentacoste, a 3^rd year PhD student in the lab is investigating lipid pathways in diatoms with hopes to identify ways to increase yields of triglycerides that could be converted to biodiesel.   

Cameron Coates, a 4^th year PhD student in the lab is investigating hydrocarbon biosynthesis in cyanobacteria.  Cyanobacteria naturally produce hydrocarbons that could be used as a jet fuel directly at about 1-2% of their dry biomass and it appears that they are making these hydrocarbons from fatty acids.  He is investigating the unique enzymes that cyanobacteria use to produce these hydrocarbons and hopes to engineer these enzymes into microbes that would eventually produce a large yield of high quality fuel that could avoid the costly and energy intensive steps of converting fatty acids and triglycerides into diesel or gasoline.  Interestingly, one of these hydrocarbon producing enzymes was discovered as a direct result of the investigations into the biosynthetic pathway for Curacin A, thus creating a direct connection between the labs work on natural products and biofuels.  It is just this type of finding that reinforces the interdisciplinary approach of the Gerwick Lab and will continue to fuel their future research for years to come.

Marine cyanobacterium Moorea producta

 

Cameron Coates is Ph.D. candidate at UCSD and a volunteer writer for SD-CAB. You can contact him at rccoates@ucsd.edu.

The Future of Fat - an SD-CAB Researcher Spotlight

by Britt Flaherty

Christine Shulse working in Puerto Rico while
collecting rare microbial samples

Christine Shulse loves fat. While I spend my day avoiding it at all costs, Christine looks for fat in new places, studies how it's made, and even thinks about engineering ways to make more fat. But Christine isn't studying the fat in my french fries – she's studying polyunsaturated fatty acids, or PUFAs, the heart-healthy fats found in expensive fish oil supplements. PUFAs are powerhouse lipids that are good for our cholesterol and have been the focus of medical studies on everything from weight loss to cancer. They can be found in fish, eggs, chicken, and healthy oils, but Christine is looking for a new and inexpensive source of heart-healthy lipids, and her work may even help us understand how to make biofuels, such as fatty-acid derived hydrocarbons.

Christine is a graduate student in Dr. Eric Allen's lab at The Scripps Institute of Oceanography, and she's discovering a source of PUFAs, a form of secondary lipids, in bacteria: "Generally I'm interested in the production of secondary lipids by microbes," she says. "Similar to secondary metabolites, secondary lipids are lipids that have not been shown to be necessary for the normal growth, development, and reproduction of these microbes under laboratory conditions. Therefore these pathways can hopefully be messed with without upsetting the cell's primary metabolism." This would allow Christine to artificially produce more or less secondary lipids in a microbe without affecting its health, which is important for engineering bugs in industrial settings. 

Christine in the Lab in San Diego

Christine studies both hydrocarbons and PUFA secondary lipids, and the synergy between the two is key: "The hydrocarbons could be used as fuel, while the fatty acids are important in human nutrition and are used as nutraceuticals. So with the knowledge of how to make that switch industry could decide which product they're interested in and then have the knowledge to optimize production of that product."

Christine's work utilizes cutting edge DNA sequencing technology and bioinformatics as well as environmental samples from all over the world, including bacteria from Lake Tyrell in Australia and even samples from 6000 meters below the ocean surface in the Puerto Rico Trench. She hopes to discover and understand energy-containing molecules that are already being made in nature and is searching for these molecules in extreme environments. "I have surveyed various environments for the genetic signatures ultimately responsible for the production of secondary lipids so that we can get an idea of the diversity and distribution of secondary lipid production in nature," she says.  She has also scanned every sequenced genome (millions of genes worth of information) from algae to cyanobacteria to protists, looking for genetic signatures of PUFA and hydrocarbon production.

 Christine analyzes every gene expressed by microbes that produce secondary lipids through high-throughput transcriptomics, or the study of gene expression in the entire organism. She looks at changes in gene expression when you change the microbe's environment, trying to decipher the triggers of lipid production. "I'm quantifying the trade-off between hydrocarbon and fatty acid production in a group of marine bacteria called Shewanella," she says.

The view from the boat in Puerto Rico

As a graduate student in an SD-CAB lab, Christine had the opportunity to present her work at the monthly SD-CAB symposium this past spring. "I love SD-CAB!" she says. "The Student and Post-Doc symposium is a great venue to polish a research presentation and also to connect with colleagues interested in the same problems." Being in SD-CAB helps her to interact with some of the best algal biotech minds in San Diego: "The feedback and questions I got when I presented at the SD-CAB symposium in January helped me publish a paper on that work in May and then present it in a more polished form at the American Society for Microbiology General Meeting in New Orleans." 

This summer, the Allen lab is even hosting an SD-CAB summer undergraduate intern, Michael Mayfield. Michael is working closely with Dr. Allen on a project that compliments Christine's work, scanning new microbes for secondary metabolite production and trying to find strains that make these important molecules. 

Christine's work and the work of the Allen group may one day leave the lab in pill or gasoline form, and while it won't make my french fries healthy, it may replace expensive fish oil supplements or help reduce the environmental impact of our energy needs.

Britt Flaherty is Ph.D. candidate at UCSD and a volunteer writer and outreach coordinator with SD-CAB. You can contact her at blflaher@ucsd.edu.