In
addition to snakes, our lab has been working on ticks
in the last decade. Ticks are blood feeding animals which
require blood meals for their survival. In order to do
this, they inject their saliva into the site of feeding
on their host.
Identification
of novel bioactive peptides from tick saliva:
Our group is interested in identifying biomolecules present
in the saliva of the ticks, particularly anticoagulant
and anti-platelet peptides. As the amount of saliva is
extremely minute and limited, we have developed an on-line
inhibition assay which is coupled to a nano-LC and mass
spectrometer. This allows us to simultaneously purify
and identify anticoagulants which are present in small
amounts in a complex mixture.
Variegin:
We have successfully isolated and characterized an anti-coagulant
peptide named variegin from the saliva of Amblyomma variegatum,
the tropical bont tick. Variegin is a potent Thrombin
inhibitor with a strong affinity for the enzyme (Ki =
10.4 pM). The three-dimensional crystal structure shows
variegin binding to the Thrombin active site and exosite-I.
Upon binding to thrombin, variegin is cleaved. This cleavage
product still retained strong binding to the thrombin
exosite-I (Ki = 14.1 nM), resulting in the prolonged inhibition
of the enzyme.
Transcriptomics
and proteomics of tick saliva:
We are also interested in the transcriptome and the proteome
of ticks, as well as the sexual differences in expression
of salivary proteins between male and female ticks.
In
collaboration with others, we have worked on toxins from
scorpion, spider, conus and fish venoms. We have
identified, isolated and characterized a number of new
toxins. We have determined their structure-function relationships
and folding determinants.
α-
and λ/χ-conotoxins
k-Hefutoxin1
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