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Entomology: Personnel

Entomology Faculty

Mark R. Brown

Professor of Entomology
Athens Campus
Ph.D., University of Georgia, 1985

Contact Information

Address: Department of Entomology
University of Georgia
413 Biological Sciences Building
Athens, GA 30602-2603

Phone: (706) 542-2317
Email: mrbrown@uga.edu

Dr. Mark Brown

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 Email
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.

Photo of hand covered by mosquitos

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.

 

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