Entomology: Personnel
Entomology Faculty
Mark R. BrownProfessor of Entomology Contact InformationAddress: Department of Entomology Phone: (706) 542-2317 |
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Courses Taught
ENTO 8250 Insect Physiology (syllabus)
ENTO 8570 Molecular Entomology (syllabus)
ENTO 8080 Topics in Insect Physiology and Biochemistry
Research Program
Please contact Dr. Brown, if you are interested in pursuing research in insect endocrinology as a graduate student. Full research/teaching assistantships are available for MS and PhD candidates.
Funding
National Institutes of Health
United States Department of Agriculture
Lab Personnel
| Name | Position | |
| Zhimou Wen | Research Scientist | zwen@uga.edu |
| Monika Gulia | Postdoctoral Associate | mgulia@uga.edu |
| Andrew Nuss | Postdoctoral Associate | nuss8@uga.edu |
| Dan Fendley | Technician | dfendley@uga.edu |
| Animesh Dhara | PhD Student | animesh@uga.edu |
Overview
Reproduction in female insects encompasses a highly regulated sequence of behavioral, metabolic, and synthetic processes that result in the production of eggs. As in all other animals, peptide hormones provide precise regulation of physiological and metabolic processes during reproduction. The primary objective of my research program is to characterize the structure and function of peptide hormones and their receptors involved in the regulation of key reproductive processes in two mosquito species: the yellow fever mosquito, Aedes aegypti, and the African malaria mosquito, Anopheles gambiae.
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Riehle, M. A., Garczynski, S. F., Crim, J. W., Hill, C. A. and Brown, M. R. 2002. Neuropeptides and peptide hormones in Anopheles gambiae. Science 298: 172-175. PDF file
Mosquitoes are exceptional model systems for this research because each successive cycle of egg maturation begins with a blood meal and ends with egg deposition two to three days later. Blood provides females with nutrients for egg maturation and metabolic storage, thus enabling survival to initiate another cycle. Understanding the regulation of reproduction in mosquitoes will give us insight into how pathogens, such as malaria and arboviruses that are ingested in a blood meal from an infected host, can multiply in the female’s body during a reproductive cycle. Then, with another meal, the pathogens are transmitted to a different host, resulting in further dissemination.
Current Projects
Collaboration with Mike Strand and Kevin Clark (UGA Entomology) and Joe Crim (UGA Cellular Biology)
Insulin-Related Peptides (ILP's)
In vertebrates, insulin and related peptides are important growth
factors and multifunctional hormones. ILPs are known for only a few invertebrate
and insect species, including mosquitoes, but their functional significance
is unexplored. Up to eight ILPs are encoded in the genome of different
mosquito species, which leads to the question, why are so many ILPs present
in a mosquito? A main objective of our research is to define the expression,
function, and signaling of all ILPs in a mosquito.
Recently, we reported that ILP3, one of eight ILPs in Aedes aegypti, stimulated yolk uptake by oocytes of blood-fed, decapitated females and ecdysteroid production by isolated ovaries. It also regulated metabolic activity by elevating carbohydrate and lipid storage when injected into sugar-fed decapitated females. Results from receptor binding and crosslinking studies showed that this ILP specifically binds to the insulin receptor in ovary cell membranes.
Krieger, M. B. J., Jahan, N., Riehle, M. A., Cao, C., and Brown, M. R. 2004. Molecular characterization of insulin-like peptide genes and their expression in the African malaria mosquito, Anopheles gambiae. Insect Molecular Biology 13: 305-315. PDF file
Wu, Q. and Brown, M. R. 2006. Signaling and function of insulin-like peptides in insects. Annual Review of Entomology 51: 1-24. PDF file
Riehle, M. A., Fan, Y., Cao, C., and Brown, M. R. 2006. Molecular characterization and developmental expression of insulin-like peptides in the yellow fever mosquito, Aedes aegypti. Peptides 27: 2547-2560. PDF file
Brown, M. R., Clark, K. D., Gulia, M., Zhao, Z., Garczynski, S.F., Crim, J. W., Suderman, R. J., and Strand, M. R. 2008. An insulin-like peptide regulates egg maturation and metabolism in the mosquito Aedes aegypti. Proceedings of the National Academy of Sciences USA 105: 5716-5721. PDF file
We first showed that vertebrate insulins stimulate steroidogenesis and protein synthesis in mosquito ovaries and identified an insulin receptor in ovaries. Activation of steroidogenesis in ovaries is through a conserved insulin signaling pathway. Expression of the insulin receptor and a serine/threonine kinase, Akt – an important regulatory nexus – were characterized during development and egg maturation in female Aedes aegypti.
Graf, R., S. Neuenschwander, M. R. Brown, and U. Ackermann. 1997. Insulin mediated secretion of ecdysteroids from mosquito ovaries and molecular cloning of the insulin receptor homologue (MIR) from ovaries of bloodfed Aedes aegypti. Insect Molecular Biology 6: 151-163. PDF file
Riehle, M. A. and Brown, M. R. 1999. Insulin stimulates ecdysteroid production through a conserved signaling cascade in the mosquito Aedes aegypti. Insect Biochemistry and Molecular Biology 29: 855-860. PDF file
Riehle, M. A. and Brown, M. R. 2002. Insulin receptor expression during development and a reproductive cycle in the ovary of the mosquito Aedes aegypti. Cell and Tissue Research 308(3): 409-420. PDF file
Riehle, M. A. and Brown, M. R. 2003. Molecular analysis of the serine/threonine kinase Akt and its expression in the mosquito, Aedes aegypti. Insect Molecular Biology 12(3): 225-232. PDF file
Ovary Ecdysteroidogenic Hormone (OEH)
This neurohormone is the functional equivalent of follicle-stimulating
hormone and luteinizing hormone in vertebrates. Neurosecretory
cells in the brain secrete OEH into the hemolymph of females
after a blood meal, and it stimulates their ovaries to secrete
ecdysteroid hormones. In turn, ecdysteroids stimulate the
production of yolk proteins, which are stored in mature eggs
and used during embryonic development. The receptor for
OEH and its mode of action are unknown, and it likely has other
functions, since it is present in males and earlier life stages.
Brown, M. R., R. Graf, K. M. Swiderek, D. Fendley, T. H. Stracker, D. E. Champagne, and A. O. Lea. 1998. Identification of a steroidogenic neurohormone in female mosquitoes. Journal of Biological Chemistry 273: 3967-3971. PDF file
Brown, M. R. and C. Cao. Distribution of ovary ecdysteroidogenic hormone I in the nervous system and gut of mosquitoes. 13 pp. Journal of Insect Science 1.3—Online journal. PDF file
Hormonal Regulation of Ovarian Ecdysteroid Production
We
are identifying proteins and enzymes involved in the biosynthesis
of ecdysteroid hormones in the mosquito ovary. A primary
focus is to determine whether the expression or activity of selected
proteins is affected by ILPs and OEH.
Sieglaff, D. H, Duncan, K. A., and Brown, M. R. 2005. Expression of genes encoding proteins involved in ecdysteroidogenesis in the female mosquito, Aedes aegypti. Insect Biochemistry and Molecular Biology 35: 369-514. PDF file
Brown, M. R., Sieglaff, D. S., and Rees, H. H. 2009. Gonadal ecdysteroidogenesis in Arthropoda: occurrence and regulation. Annual Review of Entomology 54, Reviews in Advance online. PDF file
Nutrient and Endocrine Regulation of Mosquito Development:
Collaboration with Aparna Telang (University of Richmond, Biology)
We
are unraveling how the endocrine system responds to different
nutrient states in mosquito larvae and regulates metamorphosis
and reproduction. Results from this work may provide insights
into better ways to control mosquito populations in the field.
Telang, A., Yiping, L., Noriega, F. G., and Brown, M. R. 2006. Effects of larval nutrition on the endocrinology of mosquito egg development. Journal of Experimental Biology 209: 645-655. PDF file
Telang, A., Frame, L., and *Brown, M. R. 2007. Larval feeding duration affects ecdysteroid levels and nutritional reserves regulating pupal commitment in the yellow fever mosquito Aedes aegypti (Diptera: Culicidae). Journal of Experimental Biology 210: 854-864. PDF file
Effects of insulin signaling on mosquito longevity and
immunity: Collaboration
with Mike Riehle (University of Arizona, Entomology) and
Shirley Luckhart (University of California, Davis, Medical Microbiology and Immunology)
Malaria
parasites must develop for up to two weeks in the mosquito, and conceptually,
this development can be disrupted by enhancing mosquito innate immunity or by
shortening the mosquito’s
lifespan. Our work shows that exogenous insulin in the
blood meal not only modulates lifespan and oxidative stress response
in female mosquitoes, but also Plasmodium development. We
are characterizing in detail the effects of exogenous human insulin
and insulin-growth factors on key processes related to aging,
innate immunity, and signaling in the mosquito Anopheles
stephensi for comparison to transgenic mosquitoes expressing
active proteins involved in insulin signaling.
Other Peptide Hormones of Interest
Head Peptide
This is the first neuropeptide
to be isolated from mosquitoes, and it is a member of the extensive “RFamide” family
of animal neuropeptides. This peptide inhibits the
host-seeking behavior of female Ae. aegypti, but its receptor
and mode of action have yet to be identified.
Brown, M. R., M. J. Klowden, J. W. Crim, L. Young, L. Shrouder, and A. O. Lea. 1994. Endogenous regulation of mosquito host-seeking behavior by a neuropeptide. Journal of Insect Physiology 40: 399-406. PDF file
Stracker, T. H., S. Thompson, G. L. Grossman, M. A. Riehle, and M. R. Brown. 2002. Characterization of the AeaHP gene and its expression in the mosquito, Aedes aegypti (Diptera: Culicidae). Journal of Medical Entomology 39(2): 331-342. PDF file
Neuropeptide F (NPF)
Many peptide hormones are extensively distributed
in both the brain and gut of vertebrates and coordinate appetite,
digestion, and many other processes. Neuropeptide Y and pancreatic
peptide are good examples, and the related NPFs are known for many
invertebrates. We were the first to isolate authentic NPFs
from different insect groups and to characterize the NPF receptor
and its signaling. In the fruit fly, NPF is an important
regulator of feeding behavior. In all insects, it likely
has other functions, especially in the gut, but for now, NPF has
no known function in mosquitoes and other insects.
Huang, Y-Q, M. R. Brown, T. D. Lee, and J. W. Crim. 1998. RF-amide peptides isolated from the midgut of the corn earworm, Helicoverpa zea, resemble pancreatic polypeptides.Insect Biochemistry and Molecular Biology 28: 345-356. PDF file
Brown, M. R., Crim, J. W., Arata, R. C., Cai, H. N., Chun, C., and Shen, P. 1999. Identification of a Drosophila brain-gut peptide related to the neuropeptide Y family. Peptides 20, 1035-1042. PDF file
Garczynski, S. F., M. R. Brown, P. Shen, T. F. Murray, and J. W. Crim. 2002. Characterization of a functional neuropeptide F receptor from Drosophila melanogaster. Peptides 23: 773-780. PDF file
Stanek, D. M., J. Pohl, J. W. Crim, and M. R. Brown. 2002. Neuropeptide F and its expression in the yellow fever mosquito, Aedes aegypti. Peptides 23: 1367-1378. PDF file
Garczynski, S. F., J. W. Crim, and M. R. Brown. 2005. Characterization of neuropeptide F and its receptor from the African malaria mosquito, Anopheles gambiae. Peptides 26: 99-107. PDF file
Nuss, A. B., Forschler, B. T., Crim, J. W., and Brown, M. R. 2008 Distribution of neuropeptide F-like immunoreactivity in the eastern subterranean termite, Reticulitermes flavipes (Isoptera: Rhinotermitidae). Journal of Insect Science 8: article 68. PDF file
Short neuropeptide F (sNPF)
Genes encoding
sNPFs are expressed throughout the nervous system of mosquitoes,
and multiple peptides are processed from the propeptide. Although
their cognate receptor was identified, nothing is known about
the function of sNPF in mosquitoes.
Garczynski, S. F., Brown, M. R., and Crim, J. W. 2005. Structural studies of Drosophila short neuropeptide F: occurrence and receptor binding activity. Peptides 27: 575-582. PDF file
Garczynski, S. F., Crim, J. W., and Brown, M. R. 2007. Characterization and expression of the short neuropeptide F receptor in the African malaria mosquito, Anopheles gambiae. Peptides 28: 109-118. PDF file
Adipokinetic hormone (AKH)
This family of peptide hormones is well characterized
for insects, but until recently, nothing
was known about the distribution and function of AKH in mosquitoes. There
are two AKHs in mosquitoes, and we showed that the short AKH in
fact mobilizes carbohydrate (glycogen) stores and not lipid stores. Thus,
it is a “hypertrehalosemic” hormone – an action
similar to that of glucagon and opposite that of insulin in vertebrates. The
coordination of metabolism by this peptide and ILPs in sugar and
blood-fed mosquitoes is yet to be explored.
Kaufmann, C. and Brown, M. R. 2006. Adipokinetic hormones in the African malaria mosquito, Anopheles gambiae: Identification and expression of genes for two peptides and a putative receptor. Insect Biochemistry and Molecular Biology 36: 466-481. PDF file
Kaufmann, C. and Brown M. R. 2008. Regulation of carbohydrate metabolism and flight performance by a hypertrehalosaemic hormone in the mosquito Anopheles gambiae. Journal of Insect Physiology 54:367-377. PDF file
Summary
Our research contributes to two concepts
shared by insect and vertebrate endocrinology. First, peptide hormones, as
chemical messengers, are conserved to a high degree both in structure
and function across the phyla of multicellular animals. Second,
the nervous and digestive systems of animals use these messengers
to coordinate metabolism and homeostasis, so that development and
reproduction can occur. The elucidation of key regulatory
pathways in mosquitoes can lead to stable and functional peptide
mimics or to genetic transformation that may offer a new way to
control their development or block pathogen transmission.