New Design for Biochemistry Phase II

For friends of the Department of Biochemistry at the University of Wisconsin–Madison I am pleased to send you greet- Biochemistry, plus the Ag Journalism building. At ings from the Biochemistry the time, historical preservation was limited to the Department. In the second 1912 building, which was slated to become office newsletter under my watch, space. The Curry murals in the 1937 wing were to we (being Marv Wickens et be moved to new quarters in the 1912 wing. The al.) have changed the format a Ag Journalism building was viewed as suboptimal bit, bringing you more of the and structurally unsuitable for most uses. exciting science going on in The situation has changed dramatically in the From the Chair the department, as well as the interim. About 18 months ago, the entire west Betty Craig “news” to keep you abreast of side of Henry Mall, as well as all of the 1912 and your friends and colleagues. I 1937 wings facing University Avenue, was listed hope you approve, and we welcome com- as a National Historic District. The Ag Journal- ments and suggestions to make the Biochem- ism building was determined to be in better shape istry Newsletter both informative and fun. structurally than we had thought, and the state and university have been reviewing the history of our Biochemistry Phase II Biostar Building Project little neighborhood. The west side of Henry Mall “Challenges and opportunities” is an expression is actually one of the few districts on campus that commonly used these days. Although I am not par- remains true to the original campus plans. A con- ticularly fond of this phrase, I do think it charac- sensus emerged that the preservation of the heri- terizes quite well the Biochemistry Phase II Biostar tage of the district should be an important goal of Building Project, now in an active design phase. The the project, as it was in the best interests of the scope of the project, conceived over a decade ago, department, the university, and the state. is broad, encompassing laboratory space to house The architectural team from Flad and Associ- both Biochemistry faculty (e.g., the FTEs in the ates have come up with a creative design that not Enzyme Institute) and the Biomolecular Chemis- only preserves the history of the older buildings try Department; special facilities, such as chemical (and Elmer, the elm tree), but puts even the older synthesis suites; a large vivarium; and a great deal building space to exceedingly good use in ways that of much-needed classroom and teaching laboratory will invigorate Biochemistry’s teaching program. space. An architectural study completed in 1997 In effect, the 1912 and 1937 wings will become envisioned a building that would take up the foot- a dedicated teaching complex, with new auditori- print defined by the 1937 and 1956 wings of old ums, classrooms, teaching labs, a student lounge, New design for Biochemistry Phase II - "Inspired by the past, building for the future" and some office space in support of the teach- to raise the necessary funds and I hope when I ing effort. The new research tower will be built write you a year from now I can report that we on a footprint that includes the 1956 wing, have broken ground for Biochemistry Phase II. the alley between 1956 and Ag Journalism, We are all truly excited about the project, as it and the animal rooms and auditorium south will provide state of the art research facilities of the 1985 wing. The new structure will abut, for all Biochemistry faculty, while preserving and incorporate into the design, the old Ag our history. Journalism building. This research tower will house the 20-24 research labs, animal facilities, Other updates conference rooms and state of the art chemical I am pleased to report that our new IPiB (Inte- synthesis suites. A new corridor will be created grated Program in Biochemistry) graduate between the 1912/1937 complex and the new program has gone through all of the admin- research tower, facilitating pedestrian traffic in istrative hoops and is now official. In reality this part of campus. we have been acting like it was official for the past year, recruiting together this spring with the faculty of the Department of Biomolecular Chemistry, for what has become our first IPiB class. Ivan Rayment has taken on the job of 1985 Biochem being chair of the IPiB steering committee and 2010 is busy smoothing the road of integration of Research the two graduate programs into one. Biochem Addition, 1998 Thisyear we are pleased to welcome Doug Weibel into the department as a new Assistant Professor. Doug, who has his lab on the fourth floor of the Biochemistry Addition, comes to us 2010 from Harvard Medical School as a cluster hire Teaching in chemical biology. Learn more about Doug Henry and his research on page 4. While welcoming Mall new people into the department, we also need to say goodbye to Bill Reznikoff(see page 10) who, come July 1, will retire after 37 years as a University Avenue Biochemistry faculty member. We are all sorry to see him go. We wish him all the best, and are The plan is ambitious, and will enable the glad to know that he will continue his science, department to enhance its research and teach- but his lab will be on Cape Cod, rather than ing missions over the next decades. The added next to Lake Mendota. cost to renovate the older buildings and the high Our good friend and jack-of-all-trades, Al rate of inflation of construction costs over the Jones (see page 5) is also retiring after many past 2-3 years has left us with a gap in funding great years with us and we wish him well. estimated to be about 12 million dollars out I hope you all a happy and productive year. of the total budget of 117 million dollars for Remember, we are happy to hear from you the project. We are embarking on a campaign anytime, and visit us when you can. If you would like to learn more about the exciting new building project, please feel free to contact: Elizabeth Craig, Chair Marilyn Boland, Director of Development Department of Biochemistry or University of Wisconsin Foundation Phone: 608-262-3040 Phone: 608-890-1230 [email protected] [email protected] Links Between Obesity and Diabetes by Professor Alan Attie Although most people with type 2 diabetes are (PDGF), a protein that plays an important role obese, most obese people do not develop diabe- in the formation of the vasculature. Cells requir- tes. This dichotomy has inspired us to ask: what ing new vasculature produce vascular endothelial are the genetic differences between people who are growth factor (VEGF), which recruits endo- susceptible to obesity-induced diabetes and those thelial cells to the tissue. Endothelial cells form who are resistant? We also want to identify the tubes, the precursors of blood vessels. They also pathways that trigger the transition to diabetes. produce PDGF, which recruits pericytes (a cell Obese people are insulin-resistant, meaning resembling a smooth muscle cell) to coat the that their cells do not respond fully to normal basolateral side of the vessel. insulin levels. They usually compensate for insu- Mice with the diabetogenic allele of SorCS1 lin-resistance by producing more insulin. This can have vascular abnormalities, while their congenic occur by increasing the insulin secretion from each counterparts do not. To corroborate these find- pancreatic beta cell and/or through the expansion ings, we have turned to zebrafish, another ver- of beta cell mass. However, in type 2 diabetes, tebrate with powerful genetics: zebrafish with this compensatory insulin response is inadequate reduced SorCS1-activity do indeed have dramatic and the gap between demand for insulin and the vascular abnormalities. supply of insulin leads to diabetes. If the gene really is critical in the onset of diabetes in people, we might be able to see that Identifying a new gene in natural human populations. In collaboration We have reproduced the obesity/diabetes dichot- with groups in Los Angeles and San Antonio, we omy in mice. We study two mouse strains that have found that variation in the SorCS1 gene is have been made obese using a mutation that dis- associated with diabetes in Mexican-Americans. rupts the normal suppression of appetite; the two Other groups are determining whether or not this strains differ in their susceptibility to diabetes. To gene is involved in diabetes in other populations. identify the key genes responsible, we mapped several genes that control glucose and insulin Dieting and diabetes levels. This past year, we positionally cloned one Another route to understanding the onset of dia- of these. betes has come from analyses of mRNAs present The gene is SorCS1, a member of the vacu- in obese vs normal mice. DNA microarray tech- olar protein sorting-10 (vps10) gene family. The nology allows one to survey the entire popula- protein binds to platelet-derived growth factor tions of mRNAs in a cell or tissue. Using that approach, we discovered that the cholecystokinin (CCK) gene is massively upregulated in beta cells of the pancreas obtained from obese mice. What makes this interesting is that our studies also sug- gest that CCK is a mitogen for those same beta cells. Thus, CCK appears to be an autocrine reg- ulator of the beta cell expansion that occurs when an animal is insulin-resistant and obese. Relevant publications Lan, H. Chen, M., Byers, J.E., Yandell, B.S., Stapelton, D.S., Mata, C.M., Mui, E.T., Flowers, M.T., Scheuler, K.L., Manly, K.F., Williams, R.W., Kendziorski, C.M., Attie, A.D.

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