Faculty & Staff
Gregory Beck, PhD
Associate Professor of Biology - Immunology
Areas of Expertise
PhD, State University of New York at Stony Brook, 1994.
BS, University of SUNY Albany, 1982.
Professional Publications & Contributions
- Associate Member, Dana-Farber/Harvard Cancer Center (DF/HCC).
- Adjunct Associate Professor, Intercampus Graduate School of Marine Sciences and Technology, University of Massachusetts-Boston.
My laboratory is applying contemporary techniques of biochemistry and molecular biology to an important emerging field in biomedicine: the evolution of the immune system. Our investigations build upon the discoveries that key immunoregulatory mechanisms that function in the mammalian immune response appear to be present in phylogenetically distinct invertebrate species. The wide distribution of such basic elements of innate host defense responses demonstrates their antiquity in animal evolution. By studying host defense mechanisms in lower animals, we may be able to unravel the complex web of interactions among cells and factors of vertebrate immune responses and help identify common mechanisms and novel strategies.
Investigating the mechanisms of primitive animals strategies to thwart affronts to homeostasis will surely shed light on the ways in which the vertebrate body deals with similar threats to survival. My long-term goals are to unravel the defense reactions employed by invertebrates. Studies of ancient defense systems have extensive implications for understanding the evolution of immunity and problems of human health and disease.
The 3 major research interests of my laboratory are listed below:
1) Toll Receptors
The recognition and subsequent clearance of pathogens from the body requires a very coordinated and time-dependent response. One of the first lines of defense against pathogens involves the innate immune response. Innate immunity involves anatomical, physiological, phagocytic and inflammatory barriers redeployed before infection, are capable of rapid response to pathogens, and react in mostly the same way to repeated infections. Innate immunity involves recognition of molecular patterns on the surface of pathogens. These patterns [termed pathogen associated molecular patterns (PAMPs)] are common constituents of many pathogens. Examples of PAMPs include lipopolysaccharide (LPS), lipoproteins, peptidoglycan, chitin, and bacterial flagellin. Therefore, the cells and molecules of the innate immune system can react and phagocytize the pathogens immediately upon recognition, irrespective of prior exposure. Molecules on the surface of vertebrate immune cells called pattern recognition receptors (PRRs) are involved with the detection of PAMPs. Toll-like receptors (TLRs) are one of the major PRRs and are one of the first sentinels to communicate infection in innate immunity. First discovered in Drosophila as regulators of dorso-ventral patterning in embryogenesis, they have subsequently been found to play an integral role in the recognition and removal of pathogens. The TLRs shows striking similarities in plants, invertebrates, and vertebrates. Thirteen mammalian/human TLRs have been described.
The TLRs are transmembrane proteins characterized primarily by leucine-rich repeat (LRRs) motifs in their extracellular portions and a cytoplasmic Toll-interleukin receptor (TIR) domain. The LRR motif is very ancient and is found in many organisms such as viruses, bacteria, plants, fungi and animals. In general, LRRs are typically involved in cell adhesion and recognition. Each repeat consists of about 19-29 amino acids and forms an N-terminal region of hydrophobic residues usually composed of leucines. Multiple repeats together create a horseshoe-shaped solenoidal structure, which is directly involved in ligand interaction. The TIR domain is evolutionarily ancient in origin as well and is found in most eukaryotes (and a small number of bacteria and viruses). It contains three highly conserved regions, and mediates protein-protein interactions between the TLRs and signal-transduction components (i.e., activation of the NF-kB pathway).
The focus of this project is to isolate and characterize TLRs in the Leidy’s Comb Jelly (Mnemiopsis leidyi) and Moon Jellyfish (Aurelia aurita). The isolation and study of TLRs from invertebrates should have implications in understanding the evolution of immunity as well as in developing new drugs to help in the fight against human diseases.
2) Antimicrobial peptides and proteins
Antimicrobial peptides (AMPs) are a class of small cationic molecules [molecular weight (Mr), ≈ 10 kDa. These molecules have been found to possess anti-viral, anti-bacterial and anti-cancer activities as well as contributing to innate immune response. There are currently over 900 known AMPs that have been isolated from plants, animals and bacteria (a complete list of these AMPs can be found at http://aps.unmc.edu/AP/main.php). The AMPs work primarily by targeting negatively charged lipopolysaccharide in the bacterial membranes. This is where killing begins. In order for an AMP to be successful at eliminating a pathogen, its chemical effects must react faster than the bacteria can grow. The first AMP isolated from insects was cecropin. Defensins, another AMP, are found in various organisms including mammals, insects and plants. Other AMPs have been found in almost every organism (i.e., bacteria, amphibians, mollusks, arthropods, fish). Microbes often do not recognize AMPs since they are capable of binding to and destroying lipopolysaccharide and or peptidoglycan. Bacteria therefore have very limited defense against AMPs and proteins. The AMPs are classified by their structure: alpha helical, beta sheet, loop and extended peptides. Alpha helical and beta sheet AMPs are most commonly found in nature, however all four types may be synthetically produced. Not only are AMPs characterized by their chemical structure they are also classified by their location and site of activity within an organism. They can be found in internal fluids (such as lymph), phagocytic cells and mucosal surfaces.
Lysozyme, is an antimicrobial protein found in most all biological fluids and tissues, (i.e., milk, tears, saliva, airway secretions). Lysozyme is biologically important for self-defense against microbial infections and is more effective at eliminating infections caused by gram-positive bacteria. Some other functions of lysozyme include killing of viruses, tumors and immune modulatory and anti-inflammatory activities. Lysozymes typically have a high isoelectric point, are heat stable, and have low Mr ranging from 11-22 kDa. Lysozymes have been found in numerous organisms ranging from microbes to plants and animals. As a result, lysozyme has been categorized into several classes that include chicken, goose, insect, phage, plant and bacteria type lysozymes. Each class differs by its amino acid sequence, molecular weight and enzymatic properties.
Lysozyme has been found in invertebrates (e.g., oysters, shrimp, Drosophila, starfish, bivalves, conch and earthworms). These lysozymes have been found to be of either the chicken (c), goose (g) or invertebrate type (i). It has been estimated that both the c and i type lysozymes have been in existence for over 600 million years. Studies have revealed that i-type lysozyme is more closely related to g-type lysozyme whilst c-type lysozyme seems to be more ancestral to both g and i-type lysozymes. The i-type lysozyme has been found in nematodes, echinoderms, annelids and mollusks.
The aim of this work is to isolate and characterize antimicrobial peptides and lysozyme in the body fluids and mucus secretions of Ctenophores (Leidy’s Comb Jellyfish; Mnemiopsis leidyi) and Cnidaria (Moon Jellyfish, Aurelia aurita). We hope these studies may provide a new avenue by which therapeutics can be developed not only for human medicine but also for agriculture and aquaculture.
3) Sea Urchin (Diadema antillarum) Immune Responses
In 1983 the black-spined sea urchin (Diadema antillarum) began to vanish from the Caribbean Sea, disappearing first from coral reefs close to the Panama Canal and eventually from almost every coral reef in the Caribbean by 1984. This mass mortality, which wiped out more than 97% of the Caribbean-wide Diadema population, was one of the most devastating mortalities ever recorded for a marine animal. This die-off is a major factor leading to a phase shift from coral-dominated to algae-dominated communities that has occurred on many Caribbean reefs during the past 20 years. In St. Croix, the density of Diadema before the 1983 die-off was estimated to be ≈6.4 individuals/m2. In 1984, densities plummeted to <0.1 individuals/m2, and in 2001 there were ≈0.17 individuals/m2. Decades after the mass mortality event, Diadema was still rare, with very low recruitment rates.
It is thought that the demise of Diadema was caused by a water-borne pathogen. Indeed, the systematic syndrome was the same at all sites, and plots of surface currents in the Caribbean Sea coincide significantly with the spread of the Diadema die-off. In addition, several species of bacteria capable of killing Diadema were isolated from urchins that were dying in the laboratory, but were not definitively associated with individual urchins in the field that were killed.
Recent recovery of Diadema has been associated with reductions in algal cover and increased coral recruitment success in Jamaica, and with reductions in algal cover in St. Croix, where Acropora palmata colonies are reappearing in areas with high Diadema densities, but are largely absent where Diadema are absent or uncommon. Recovery of Diadema may be critical to restoration of coral communities, particularly where reefs have few herbivorous fishes due to heavy fishing, as in the USVI. Many factors may be influencing Diadema recovery, including predation, competition from other herbivores, and effects of rarity (low reproduction and recruitment stemming from low population density). Another factor that must be considered is possible immunological weakness of this Diadema population which would allow continuing morbidity or mortality due to the original mass mortality pathogen or other diseases. Understanding of recovery dynamics may be improved by studying the relationship between demographic features and the basic immunological condition of Diadema populations.
Our current studies are aimed at uncovering basic features of the immunological responses of Diadema: What are the basic features of the immunological responses of Diadema? How does strength of immune responses in Diadema compare to other Caribbean urchins that did not die off (e.g., Tripneustes ventricosa, Echinometra lucunter, or Echinometra viridis)? Are there immunological differences in local populations of Diadema on St. Croix that could be related to site-specific speeds of recovery?
Current Grant Support
- PADI Foundation: Compromised Immunity and a Marine Epidemic: The Mass-Mortality of Diadema. Principal Investigator, 6/1/10-5/30/11, $5,730.
- NSF: Planning Grant for Program and Facility Enhancement for the UMass Boston Nantucket Field Station. Co-Principal Investigator, 11/15/10-11/14/13, $25,000.
Patents Applied and Pending
The Research Foundation of State University of New York Technology Transfer Office, Albany NY.
- No. R-333, Borrelia burgdorferi spirochetal LPS.
- No. R-462, Monoclonal antibodies specific for Borrelia burgdorferi LPS.
The University of Massachusetts Office of Commercial Ventures and Intellectual Property, Worcester, MA.
- An anti-inflammatory mediator from Cucumaria frondosa.
- An antimicrobial peptide from Cucumaria frondosa.
- Antibody microarray for environmental monitoring.