Researchers in the Center for Marine Biotechnology and Biomedicine (CMBB) at Scripps participate in fundamental studies of the physiology of marine organisms, the conservation and management of marine habitats, the development of environmental monitoring and remediation technologies, the design of model systems to supplement mammals in biomedical research, the characterization of marine toxins and pollutants, and the development of pharmaceuticals from marine organisms.
New Cures from the Sea
With 20 government-approved marine derived or inspired drugs on the market, the promise of the sea to provide new pharmaceuticals is becoming a reality. CMBB researchers have helped discover the vast biomedical potential of life in the world’s oceans and along the way have developed new chemistry tools to accelerate the discovery process. In collaboration with industry partners, CMBB scientists are actively researching and developing new anticancer, antibiotic, and antiviral medications – including COVID-19 therapies – derived from marine microorganisms and their amazing arsenal of bioactive natural products.
Explaining Human Disease Processes and Marine Models
Marine animals have long served important roles in biomedical research. Research in these model systems has already paid huge dividends in cellular immunology, neurobiology, and embryology. Nobel prize winning discoveries have been made using marine organisms (e.g., nerve action potential; learning and memory; regulation of cell division). Studies in marine animals have also been the basis for transformative technological advances, such as the ability to utilize naturally fluorescent proteins to visualize individual proteins in vivo and in real time. Research by CMBB scientists has leveraged marine organisms to uncover new roles of proteins important for elimination of drugs and toxicants from humans. This work has also led to discoveries about how marine pollutants found in seafood affect these pathways. CMBB scientists are also developing new marine experimental systems for studying the brain circuits controlling behavior, identifying the proteins necessary for biomineralization, and uncovering novel ways in which genomes control the construction of complex multicellular organisms.
The world’s oceans harbor immense microbial diversity. Researchers at CMBB are using both culture-dependent and culture-independent techniques to explore this diversity and develop new methods to harness their unique adaptations for biotechnology. This ranges from biofuel development and marine aquaculture to pharmaceutical discovery. One success story is salinosporamide A (marizomib), which was discovered at Scripps, licensed to Bristol-Myers Squibb, and has now entered phase III clinical trials for the treatment of cancer.
Using Genetics to Produce Marine Pharmaceuticals
Research by CMBB scientists has decoded how marine microbes produce potent chemicals that can be transformed into pharmaceuticals. New genetic technology developed at Scripps now makes it possible to readily transfer genetic material from one organism to another, thereby allowing the convenient production of marine pharmaceuticals in laboratory engineered microbial factories. The engineered production of the seaweed chemical kainic acid used in brain research is a recent success story of CMBB scientists.
Harmful Algal Blooms and Marine Toxins
Massive oceanic blooms of toxic algae have increased in frequency in recent decades, including along the California coastline. Scripps scientists are studying how and why marine microorganisms bloom in the ocean to produce toxins harmful to marine animals and humans. Combining new genomic tools with modern ocean robots is transforming the way in which we monitor and predict harmful algal blooms.
Researchers at Scripps are exploring how the dynamics of microbial communities, known as microbiomes, are shaping the resistance and resilience of marine ecosystems and organisms to stress. Also, host-associated microbiomes found in model organisms that can be manipulated in the lab are helping us test fundamental hypotheses about how bacteria and viruses can alter human health by producing immune responses, shaping embryonic development, and by production of small molecules which affect how we fight infection, our metabolism, and even our neurobiology.
Studies in Marine Mammal and Seabird Physiology
Anatomical and physiological adaptations of marine mammals and seabirds underlie their diving behavior and foraging ecology. They are especially important to their survival in an era of changing ocean temperatures, shifts in prey distribution, and anthropogenic disturbances (ship noise, sonar, etc.). Diving physiology can also provide insight into basic physiological principles and potential therapies for human disease. In regard to medicine, diving physiology is particularly relevant to pulmonary and cardiovascular function, and to the pathology and potential treatment of patients with hypoxemia and/or ischemia. Over the past 60 years, Scripps researchers have investigated cardiovascular and respiratory function as well as diving behavior and ecology in seals, sea lions, dolphins, and penguins. Recent fieldwork has ranged from populations censusing and documentation of deep-diving behavior of emperor penguins in the Ross Sea to the investigation of the electrocardiogram and heart rate regulation in the world’s largest animal, the blue whale.
Genomics, the study of an organism’s entire complement of DNA, is synonymous with modern biology. CMBB researchers are applying cutting-edge genomic technologies to explore the diversity and genetic potential of marine organisms, from microbes to metazoans. In collaboration with technologists at allied local institutes, including the J. Craig Venter Institute, Salk Institute, and the Institute for Genomic Medicine, CMBB scientists are decoding the genetic repertoire of the ocean’s biology using high-throughput data platforms, advanced bioinformatic strategies, and high-performance computing resources. These data rich products are being co-opted to identify biosynthetic gene clusters involved in the production of bioactive compounds and to track genetic signatures of marine organisms through space and time.
Fruit flies of the sea: Transgenic marine organisms
The vast majority of biological knowledge has been derived from studying only a few model organisms. Common features of these animal models – such as ease-of-use in the laboratory, high fecundity, and rapid reproduction – have enabled researchers to leverage genetics, genomics, and functional manipulation of genomes and proteomes to understand function. The current animal model organisms represent, however, only a small sampling of animal diversity on the Planet. A significant gap in coverage exists for the vast diversity of marine animals, from which metazoan life originated and where the most animal phyletic diversity is found. CMBB researchers are building community resources devoted to the high-level production of transgenic sea urchins, prioritized by their scientific and biomedical importance. Using CRISPR modern gene editing technologies, CMBB researchers are now able to make transgenic lines suitable for using these animals to solve problems of growing biomedical importance.