Research
Area
• Insect
immunity: biochemistry, molecular biology and function of
immune-related genes
• Signal
transduction pathways: regulation of the
expression of antimicrobial peptide genes
• Structural biology:
protein-protein/ligand interactions
Research
Interest
I.
Insect Immunity: Insects
have an effective and rapid immune system against microbial infections,
which is similar to the innate immune system of vertebrates. Insect
immunity is also composed of humoral and cellular immune responses. In
insect cellular immune responses, hemocytes (blood cells) are involved
in phagocytosis of microbes,
hemocyte nodule formation, and encapsulation of large pathogens;
while humoral immune responses include synthesis of antimicrobial
peptides, blood clotting
system, and activation of the prophenoloxidase
cascade leading to melanization. Research in my lab
has been focused on how recognition process triggers different immune
responses in a model insect, the tobacco hornworm, Manduca sexta.
II. Pattern Recognition
Receptors in Innate Immune Responses: Recognition
of pathogens and differentiation of nonself from self molecules are the
first and critical step for animals to mount an immune response.
Insects lack antibody molecules. Therefore, recognition of nonself is
achieved by pattern recognition, a process mediated by a set of pattern
recognition receptors (PRRs). These PRRs specifically recognize and
bind to the molecular patterns, called pathogen-associated molecular
patterns (PAMPs) (such as lipopolysaccharide, lipoteichoic acid and
peptidoglycan from bacteria, and beta-1,3-glucan from fungi) present on
the surface of microorganisms. Recognition of PAMPs by different PRRs
will trigger a variety of immune responses including phagocytosis,
nodule formation, encapsulation and melanization. My
lab is focused on immulectins (IMLs), members of the C-type
(calcium-dependent) lectin superfamily, as pattern recognition
receptors involved in phagocytosis,
encapsulation and melanization.
III. Signal Transduction Pathways in Activation of
Antimicrobial
Genes: Insects
synthesize
a group of antimicrobial peptides. Activation of these antimicrobial
genes
can be triggered by microbes or microbial components, and is mediated
by
signal transduction pathways. PRRs may be involved in the upsteam
recognition
process of the pathways. My research is to
understand
how immulectins are involved in the recognition process to transduce
signals into cells to activate antimicrobial genes.
IV. Protein-Protein/Ligand
Interactions:
Immulectins
(IMLs) are C-type lectins, each IML contains two
carbohydrate-recognition
domains (CRDs). IMLs bind to bacterial cell wall components such as
lipopolysaccharide
(LPS) and lipoteichoic acid (LTA). They also interact with other plasma
proteins,
for example serine proteinase homologs (SPHs), a group of proteins with
similarities to serine proteases. SPHs are
unlikely
to have proteolytic activity, because
the
active site serine residue in the proteinase-like domain of SPHs are
mutated to glycine. But SPHs are required for activation of proPO by
prophenoloxidase-activating protease (PAP). In the absence of SPHs,
active PAP can not convert
proPO to its active form PO. However, in the presence of SPHs, proPO
is cleaved by PAP to produce functional enzyme PO. Research
in this lab is to understand how IMLs initiate and mediate protein-protein interactions to
form
a functional protein complex in activation of proPO.
V. Encapsulation and Melanization of Parasites: Blood-feeding insects can act as vectors for
parasites, which cause human diseases such as malaria, sleeping
sickness, lymphatic filariasis and river blindness. To transmit the
diseases, parasites must invade the insect vector and avoid or suppress
its immune responses to complete part of their life cycles. It seems
that in insect vectors of human diseases, detection and killing of
parasites are not highly effective. A major form of immune response
against parasites in the insect vector is encapsulation followed by
melanization. We have found that IML-2
recognized and bound to the surface of
the
nematode, Brugia malayi, the parasite which causes
human
lymphatic filariasis. Our research is to
identify
the surface molecules on the nematode to which IML-2 binds, and to
understand
how binding of IML-2 to B. malayi enhances encapsulation and melanization of the nematode by M.
sexta hemocytes.
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