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Postdoctoral Position

Marcelo Jacobs-Lorena mxj3 at PO.CWRU.EDU
Thu Apr 30 15:56:03 EST 1998

Mosquito Molecular Genetics

	A postdoctoral position is open in my laboratory to study gene
expression in the mosquito. The mosquito is essential for transmission
of Plasmodium, the causative agent of malaria. When the mosquito ingests
an infected blood meal, the gut is the first site of interaction between
the insect host and the parasite.=20

	One of our objectives is to characterize gut-specific promoters. These
may be used to express anti-parasite molecules in the gut of genetically
modified mosquitoes. Most gut-specific genes characterized to date are
induced relatively late (~24 h) after ingestion of a blood meal, at a
time when the parasites are separated from the secretory epithelium by a
thick chitin-containing peritrophic matrix. However, we have recently
identified a gene that is activated strongly (~10-fold) and early (< 30
min) after blood ingestion (Edwards et al., Insect Biochem. Mol. Biol.
27:1063-1072, 1997). We are functionally characterizing the
corresponding promoter by expression in transgenic Drosophila (see Xiong
and Jacobs-Lorena, PNAS 92:9313-9317, 1995) and by introducing the gene
into mosquitoes either with retroviruses (in collaboration with Jane
Burns) or with transposable elements.=20

	Another objective is to identify genes encoding 1) components of the
chitin-containing, extracellular peritrophic matrix (a potential barrier
for Plasmodium development) and 2) =93early=94 regulatory genes
(transcription factors?) required for the activation of the =93late=94
digestive enzyme genes. By use of subtractive libraries and by
immunoscreening we have identified a gene encoding a gut-specific
chitinase (Shen and Jacobs-Lorena, J. Biol. Chem. 272:28895-28900,
1997), a gene encoding a peritrophic matrix protein hypothesized to be a
=93molecular crosslinker=94 of chitin fibrils (Shen and Jacobs-Lorena, J.
Biol. Chem., in press) and a gene encoding a major mucin-like surface
protein which is a candidate receptor for Plasmodium invasion (submitted
for publication).

	We are also using a =93phage display library=94 to define peptide sequen=
that interact with specific mosquito organs. This project may lead to
identification of host receptors used by mosquito-transmitted parasites.=20

	Malaria kills about 2 million people per year. The situation has been
worsening because of increased drug and insecticide resistance, and for
lack of an effective vaccine. Studying insect-parasite interactions may
lead to novel approaches to disease control. In addition to the high
medical relevance, it is worth pointing out that this rapidly expanding
research field has recently been receiving increased attention and
financial support from the NIH and other funding agencies.

	For further information please contact:

Marcelo Jacobs-Lorena
Case Western Reserve University =09
School of Medicine =09
Department of Genetics =09
10900 Euclid Avenue	genetics/
Cleveland, Ohio 44106-4955

Tel: (216) 368-2791
FAX: (216) 368-3432
Internet mxj3 at po.cwru.edu
Web site: http://meds20547.meds.cwru.edu/dept/

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