Current research projects
Packing up DNA in sperm and embryos
The DNA in sperm is special. It is uniquely packaged and segregated in comparison to other developmental time periods. In addition, the transcription of genes during this period is highly regulated. Defects in any of these processes can lead to infertility. The image on the right is a dissected male gonad from C. elegans where the DNA has been stained with antibodies that recognize the sperm-specific histone variant HTAS-1. The germ cell nuclei can be seen progressing through spermatogenesis, which results in very highly compacted sperm DNA. Our goal is to understand how histone variants, like HTAS-1, function in making sperm or passing on information from the male to the new embryo after fertilization.
​
Cells undergoing sperm meiosis in C. elegans.
Blue is DNA, Green are microtubules, Red is the kinetochore.
We find the kinetochore connects microtubules and chromosomes during sperm meiosis and are retained during anaphase. This is distinct from oocyte meiosis, where kinetochores are dissembled during anaphase.
Segregating DNA during sperm formation
A key process to making sperm or eggs is to replicate and divide up DNA in a process called meiosis. Our work shows that meiosis during sperm formation is very different than oocyte formation.
In particular chromosomes are segregated using distinct molecular players, like GSP-3 and GSP-4, which are sperm-specific proteins that are critical to sperm meiotic chromosome segregation. When these proteins are missing, sperm fail to complete meiosis. We are applying proteomic, biophysical, and cell biological methods to both how sperm chromosomes move during meiosis and how GSP-3 and GSP-4 function specifically in sperm chromosome segregation.
​
References
Zinc: A small molecule with a big impact on sperm function.
Chu DS.
PLoS Biol. 2018 Jun 7;16(6):e2006204. doi: 10.1371/journal.pbio.2006204. eCollection 2018 Jun.
PMID: 29879100
​
Owens MT, Trujillo G, Seidel SB, Harrison CD, Farrar KM, Benton HP, Blair JR, Boyer KE, Breckler JL, Burrus LW, Byrd DT, Caporale N, Carpenter EJ, Chan YM, Chen JC, Chen L, Chen LH, Chu DS, Cochlan WP, Crook RJ, Crow KD, de la Torre JR, Denetclaw WF, Dowdy LM, Franklin D, Fuse M, Goldman MA, Govindan B, Green M, Harris HE, He ZH, Ingalls SB, Ingmire P, Johnson ARB, Knight JD, LeBuhn G, Light TL, Low C, Lund L, Márquez-Magaña LM, Miller-Sims VC, Moffatt CA, Murdock H, Nusse GL, Parker VT, Pasion SG, Patterson R, Pennings PS, Ramirez JC, Ramirez RM, Riggs B, Rohlfs RV, Romeo JM, Rothman BS, Roy SW, Russo-Tait T, Sehgal RNM, Simonin KA, Spicer GS, Stillman JH, Swei A, Tempe LC, Vredenburg VT, Weinstein SL, Zink AG, Kelley LA, Domingo CR, Tanner KD.
CBE Life Sci Educ. 2018 Spring;17(1). pii: ar2. doi: 10.1187/cbe.17-06-0106. Erratum in: CBE Life Sci Educ. 2018 Spring;17 (1):.
PMID: 29326102
​
Classroom sound can be used to classify teaching practices in college science courses.
Owens MT, Seidel SB, Wong M, Bejines TE, Lietz S, Perez JR, Sit S, Subedar ZS, Acker GN, Akana SF, Balukjian B, Benton HP, Blair JR, Boaz SM, Boyer KE, Bram JB, Burrus LW, Byrd DT, Caporale N, Carpenter EJ, Chan YM, Chen L, Chovnick A, Chu DS, Clarkson BK, Cooper SE, Creech C, Crow KD, de la Torre JR, Denetclaw WF, Duncan KE, Edwards AS, Erickson KL, Fuse M, Gorga JJ, Govindan B, Green LJ, Hankamp PZ, Harris HE, He ZH, Ingalls S, Ingmire PD, Jacobs JR, Kamakea M, Kimpo RR, Knight JD, Krause SK, Krueger LE, Light TL, Lund L, Márquez-Magaña LM, McCarthy BK, McPheron LJ, Miller-Sims VC, Moffatt CA, Muick PC, Nagami PH, Nusse GL, Okimura KM, Pasion SG, Patterson R, Pennings PS, Riggs B, Romeo J, Roy SW, Russo-Tait T, Schultheis LM, Sengupta L, Small R, Spicer GS, Stillman JH, Swei A, Wade JM, Waters SB, Weinstein SL, Willsie JK, Wright DW, Harrison CD, Kelley LA, Trujillo G, Domingo CR, Schinske JN, Tanner KD.
Proc Natl Acad Sci U S A. 2017 Mar 21;114(12):3085-3090. doi: 10.1073/pnas.1618693114. Epub 2017 Mar 6.
PMID: 28265087
​
Parental Control Begins at the Beginning.
Chu D.
Genetics. 2016 Dec;204(4):1377-1378. Epub 2016 Dec 7. No abstract available.
PMID: 27927904
Samson M, Jow MM, Wong CC, Fitzpatrick C, Aslanian A, Saucedo I, Estrada R, Ito T, Park SK, Yates JR 3rd, Chu DS.
PLoS Genet. 2014 Oct 9;10(10):e1004588. doi: 10.1371/journal.pgen.1004588. eCollection 2014 Oct.
PMID: 25299455
​
Verlander JW, Chu D, Lee HW, Handlogten ME, Weiner ID.
Am J Physiol Renal Physiol. 2013 Sep 1;305(5):F701-13. doi: 10.1152/ajprenal.00030.2013. Epub 2013 Jun 26.
PMID: 23804452
​
Chu DS, Shakes DC.
Adv Exp Med Biol. 2013;757:171-203. doi: 10.1007/978-1-4614-4015-4_7. Review.
PMID: 22872478
Sperm development and motility are regulated by PP1 phosphatases in Caenorhabditis elegans.
Wu JC, Go AC, Samson M, Cintra T, Mirsoian S, Wu TF, Jow MM, Routman EJ, Chu DS.
Genetics. 2012 Jan;190(1):143-57. doi: 10.1534/genetics.111.135376. Epub 2011 Oct 31.
PMID: 22042574
​
Tzur YB, Egydio de Carvalho C, Nadarajan S, Van Bostelen I, Gu Y, Chu DS, Cheeseman IM, Colaiácovo MP.
PLoS Biol. 2012;10(8):e1001378. doi: 10.1371/journal.pbio.1001378. Epub 2012 Aug 21.
PMID: 22927794
Wu TF, Nera B, Chu DS, Shakes DC.
Syst Biol Reprod Med. 2010 Jun;56(3):222-35. doi: 10.3109/19396361003749986. Review.
PMID: 20536322
​
26G endo-siRNAs regulate spermatogenic and zygotic gene expression in Caenorhabditis elegans.
Han T, Manoharan AP, Harkins TT, Bouffard P, Fitzpatrick C, Chu DS, Thierry-Mieg D, Thierry-Mieg J, Kim JK.
Proc Natl Acad Sci U S A. 2009 Nov 3;106(44):18674-9. doi: 10.1073/pnas.0906378106. Epub 2009 Oct 21.
PMID: 19846761
​
Spermatogenesis-specific features of the meiotic program in Caenorhabditis elegans.
Shakes DC, Wu JC, Sadler PL, Laprade K, Moore LL, Noritake A, Chu DS.
PLoS Genet. 2009 Aug;5(8):e1000611. doi: 10.1371/journal.pgen.1000611. Epub 2009 Aug 21.
PMID: 19696886
Sperm chromatin: fertile grounds for proteomic discovery of clinical tools.
Wu TF, Chu DS.
Mol Cell Proteomics. 2008 Oct;7(10):1876-86. doi: 10.1074/mcp.R800005-MCP200. Epub 2008 May 25. Review.
PMID: 18504257
​
Wu TF, Chu DS.
Reprod Biomed Online. 2008 Jan;16(1):13-22. Review.
PMID: 18252043
Sperm chromatin proteomics identifies evolutionarily conserved fertility factors.
Chu DS, Liu H, Nix P, Wu TF, Ralston EJ, Yates JR 3rd, Meyer BJ.
Nature. 2006 Sep 7;443(7107):101-5. Epub 2006 Aug 30.
PMID: 16943775