Drug Discovery

  • Tunicate-associated Marine Bacteria
  • Psychrophilic Glacial and Periglacial Bacteria
  • Selective Anti-parasitic Agents
  • Targeted Anti-cancer Agents
  • Medicinal Chemistry

Chemical Ecology

  • Elicitation of Silent Biosynthetic Pathways
  • Microbial Communities in Invasive Versus Native Tunicates
  • Effects of Climate Change on Microbial Chemical Ecology
  • Chemical Profiles Along Ecological Gradients

Drug Discovery

Tunicate-associated Marine Bacteria

Although considerable research has been performed related to natural product drug discovery from tunicates (also known as urochordates or sea squirts), only recently have investigators been studying the internal and surficial microbial communities associated with these members of the Chordata phylum. These tunicate-associated bacteria are likely used by the host organism for chemical defense and may thus have interesting biological properties against human pathogens. In addition, molecular genetic research has recently determined that many of the secondary metabolites previously thought to be of tunicate origin are very likely produced by symbiotic bacterial associates.

Psychrophilic Glacial and Periglacial Bacteria

The study of marine natural products from extreme environments has generally been unexplored, as most research has focused on highly biodiverse regions such as the tropics. However, exploration of extreme environments such as Polar Regions provides the possibility to encounter new microbial species with novel chemistry and with potential for biological activity against human pathogens. Most research on cold-obligate bacteria, or psychrophiles, has focused on the molecular characteristics that have allowed them to exist and in some cases thrive in extreme cold temperatures. Very little research has been done on the production of secondary metabolites by psychrophilic organisms, although genome sequencing has shown their biosynthetic potential.


Selective Anti-parasitic and Targeted Anti-Cancer Agents

Tropical neglected diseases affect millions of people each year. People who live in developing-world tropical countries are those most at risk from infection, are often those with the least socio-economic ability to obtain proper treatments, and are therefore the most likely to develop serious and often fatal illnesses. Furthermore, many tropical diseases have developed resistance to existing drugs, limiting their effectiveness. Many of the existing treatments for tropical diseases also have serious side effects that reduce patient compliance with treatment regimens or prohibit some people from receiving any treatment. Extensive and innovative drug discovery for tropical neglected diseases is necessary to reduce the global health impact of these parasitic and infectious diseases and to narrow the gap in health disparities between developed and developing countries.

One of the main challenges facing drug discovery involves preclinical and early-stage clinical failure due to the broad and unselective action of many current drug leads. Non-selective compounds have issues with clinical efficacy and safety and often lead to severe side effects that prohibit their clinical utility. To ameliorate these types of non-selective effects, future drug discovery efforts need to identify lead compounds that target cellular and/or organismal differences. Parasitic diseases present an outstanding opportunity to selectively target biological differences between protozoan and mammalian systems in order to discover therapeutic agents specifically targeted to parasitic disease vectors. In addition, the Balunas Lab focuses on finding extremely potent toxins that might serve as payloads for collaborative research on anti-cancer antibody-drug conjugates (ADCs). The antibodies that form part of the ADCs have been selected based on their ability to selectively target antigens on the surface of cancer cells over normal cells.

Medicinal Chemistry

Novel compounds with distinctive activity profiles will be considered for further research including compound scale-up to obtain sufficient quantities (re-isolation, semi-synthesis, and/or synthesis) as well as medicinal chemistry to perform structure-activity studies, with possibilities for mechanism-of-action, ADME toxicity studies, and in vivo testing. These new selectively-active compounds from or derived from marine bacteria may provide increased efficacy, ability to overcome resistance, and/or reduced side effects as compared with existing agents, and thus could be appropriate for future preclinical and clinical development.

Chemical Ecology

Elicitation of Silent Biosynthetic Pathways

Our research involves considerable focus on optimization of bacterial culture conditions (e.g., temperature, nutrients, media, light, oxygenation, and pH), with special attention on temperature as psychrophiles have previously been shown to have considerably more growth at low temperatures. We are also exploring the incorporation of chemical and physical elicitors, which may induce altered metabolite profiles. Traditional abiotic and biotic elicitors fall into two main categories: abiotic (heavy metals, UV light, and inorganic ions) and biotic (carbohydrates and oligosaccharides, fatty acids and lipids, and proteins and peptides). More recently, elicitation has begun to move in several exciting new directions that we are incorporating, most notably the use of bioactive small molecules to challenge cultures and activate silent biosynthetic pathways.


Microbial Communities in Invasive Versus Native Tunicates

We study the bacterial communities from native and invasive ascidians at various life stages and to compare their production of toxic secondary metabolites in an attempt to determine if invasive species are more heavily chemically defended and thus are not consumed by native predators. Minimal research comparing these microbial communities has been performed and no comparison of the toxicity profiles in these two communities has been done. This research has the potential to inform future research and management decisions when considering invasive ascidians as fouling agents on ships entering the LI Sound. We are gathering baseline data on the status of ascidian microbial communities in LI Sound to assist in measurement and monitoring of ecosystem changes through time. As a prominent fouling agent in the LI Sound, the study of invasive ascidian microbial profiles helps us to understand the diversity and distribution of the bacterial associates in these aquatic nuisance species. With this data we also hope to better understand the ecological impacts of invasive ascidians as we consider their effects on native species that act as food sources for commercially relevant fish populations.

Effects of Climate Change on Microbial Chemical Ecology