Thesis defense of Matt Marcello

One of our own, Matt Marcello, will be presenting his thesis defense talk:

Insights into Mammalian Sperm-Egg Adhesion and Fusion from Studies of Knockout Mouse Models of Male Infertility

Friday, December 18, 2009, 2:30 P.M.
Sheldon Hall in the School of Public Health

I'll admit that is quite the shameless plug on my part, since Matt is in my lab -- but I'll be doing these announcement for all our RB trainees' defenses! (Matt is just the first since the blog started.)

December 15, 2009 meeting

Elizabeth Ables from the Drummond-Barbosa lab will be presenting. She has a picked a paper that hits on numerous hot issues in reproduction! (Heck, my fingers got tired typing the labels for this post!) This one should be interesting -- although maybe not the best one to have in advance of the holiday eating season ...

Main paper:
Starvation Protects Germline Stem Cells and Extends Reproductive Longevity in C. elegans
Angelo and Van Gilst
Science, 2009, 326:954-958

Complementary papers:
Perspective paper - "Strategies to get arrested," Science, 326:944-945
Another research paper - Two chemoreceptors mediate developmental effects of dauer pheromone in C. elegans, Kim et al., Science, 326:994-998

Elizabeth's commentary on why she picked this:
"In their publication, Angelo and Van Gilst demonstrate that C. elegans can undergo an adult reproductive diapause (ARD) in response to starvation that delays reproduction, extends lifespan, and protects germline stem cells despite overall germline atrophy. ARD thus gives starved C. elegans adults the ability to rapidly restore the number of germ cells upon reintroduction to a food source. The authors also demonstrate that a nuclear hormone receptor, nhr-49, is required for a proper ARD response. This article caught my eye because it highlights the role of endocrine signaling as an important link between diet and reproduction ... a main focus of our work in the Drummond-Barbosa Lab."

December 1, 2009 - Trainees, meet Donna Vogel of the Professional Development Office!

We'll take a break from paper presentations on December 1 and will have a special event for trainees in the reproductive biology labs (PIs welcome too!). Dr. Donna Vogel from the Professional Development Office will come to meet with us. Donna is an MD-PhD with special ties to reproductive biology. From 1987 to 2001, she was a program director in the Reproductive Sciences Branch of NICHD. (In fact, I got to know her when she was the program officer for my first NIH grant, my NRSA post-doctoral fellowship! Some of you might know or have heard of other program directors at NICHD, such as Dick Tasca, Susan Taymans, and Stuart Moss; these are people doing the sort of NIH job that Donna used to do.) Donna next worked with the NCI, with a focus on post-doctoral fellowship programs, then was Deputy Director of the Ellinson Foundation. In 2007, she came to Hopkins and back to her passion of training and mentoring, to head the PDO.

Donna will visit on December 1 to give us a taste of her take on career development, to discuss upcoming offerings of the PDO (especially a course, called Your Research Career, coming up in January), and to answer any and all questions about science, grants, NIH, career, life, and everything. This will be a great chance for trainees to meet Donna in this small, informal setting … and as she will tell you, you can never network too much! Oh, and you should also ask her about Jeopardy! – she was a contestant and made it to the Tournament of Champions!

Nov. 17, 2009 journal club

Leesa from the Drummond-Barbosa lab will be presenting (our first presenter from that lab!). And although this isn't our first presentation on the ovary, it's been a while! The last one I remember was when we hit on the ovarian germline stem cell controvery in 2006. Interestingly, we'll be coming back to one aspect of this part of ovarian biology with:

Tsc/mTORC1 signaling in oocytes governs the quiescence and activation of primordial follicles, Human Molecular Genetics, in press
Adhikari et al.

This work also has some interesting human health relevance, as Leesa's comments note ...
"A woman's reproductive lifespan is thought to be partially determined by the number of primordial follicles she has at birth. Primordial follicle are maintained in a quiescent state until puberty, at which point they begin to develop into ova and that 'biological clock' starts ticking away. Menopause occurs when the pool of follicles becomes exhausted. But what happens if the clock starts ticking too early? This paper from the Liu lab in Sweden investigates the signaling pathways necessary to maintain primordial follicles in a resting state in mice and finds that insulin and TOR signaling are both necessary, but not sufficient for this process. Over-activation of either pathway leads to premature ovarian failure, or POF. This study is of particular relevance to my work in the Drummond-Barbosa lab. A female Drosophila's reproductive lifespan is determined by how long her ovarian germline stem cells, or GSCs, can be maintained in the niche to produce eggs. Our lab has demonstrated that both insulin signaling and TOR signaling levels (both highly conserved pathways in structure and function) are required for GSC maintenance, and perturbation of either pathway leads to POF. Hope to see you there!"

Nov. 3, 2009 meeting

Becca from the Matunis lab will be presenting (12:30 in W2303 in the SPH).

Two-step oligoclonal development of male germ cells; PNAS 2009, 106:175-180
Ueno, Turnbull, and Weissman
Weissman lab profile here
Hot off the presses (FYI) - a profile on Weissman in the brand new issue of JCB

Becca's comments on this paper choice -
"This paper uses tetrachimeric mice to mark and study the development of the male germline and finds that the entire lineage is derived from a mere 4 cells. One of my projects is to characterize the primodial germ cell (PGC) to germline stem cell (GSC) transition in Drosophila embryos. It has long been known that, in Drosophila, the number of PGCs initially incorporated into the gonad is greater than the number of GSCs, suggesting that some sort of selection process occurs. This paper suggests that there are parallel themes in mammals, where germ cells that actually contribute to adult spermatogenesis also arise from a smaller, perhaps select few, cells within a pool of potential founder cells."

Oct. 20, 2009 meeting - the Y chromosome makes an appearance

Rachel from the Matunis lab will be presenting at the Oct. 20 meeting (12:30, W2303 in the SPH).

Cell, 2009, 138:855-869
Isodicentric Y chromosomes and Sex Disorders as Byproducts of Homologous Recombination that maintains Palindromes
Lange et al. (David Page lab)

This paper has also gotten a number of highlight write-ups (e.g., The Scientist, ScienceDaily). Since the RBJC blog started last year, this will be our first meeting on the Y chromosome and on science related to sex determination pathways (yay for new post labels!). This should be an interesting step back from the biology of the testis (which has been abundantly represented in papers presented) to the biology linked with the very first steps for getting the testis there in the first place. (Thanks, Rachel!)

Post script - Bonus points to Rachel for rallying through a cold, and for finding a comedienne who uses her Turner Syndrome as a focal point for her humor - "Dude, where's my chromosome?" [Who knew???]

Oct. 6, 2009 RBJC meeting

Phylis from the Matunis lab will be presenting (12:30 in Room W2303):

Molecular dissection of the male germ cell lineage identifies a putative spermatogonial stem cells in rhesus macaques
Hermann et al. (Kyle Orwig's lab), Human Reproduction, 2009, 24:1704-1716

Phylis admits that this paper does not relate to her research directly, "but I picked it because it helps shed some light in the characterization of spermatogonial stem cells in primates, in this case the rhesus macaque. Some work has already been done in rodents, goats and dogs in the identification and transplantation of their spermatogonial stem cells. In non-human primates, much remains to be learned." She'll also include a bit about her research on using cell death to disrupt the balance between the cells in the Drosophila testis niche.

Sept. 22 RBJC - cancelled

Our fearless presenter has flu-like symptoms, and the edict is stay home until you're symptom-free for 24 hr. Protecting health, saving lives, millions at a time (or at least the couple dozen he would have exposed at journal club). Stay tuned for details on our October 6 journal club!

RBJC fall 2009 location - Room W2303 in the School of Public Health

See map for the approximate location of Room W2303.

Please be forewarned that there is another group in the room up until 12:30. Given this, whomever is presenting will only be able to get in the room to get set up with the projector right at 12:30, so presentations will probably start ~12.35. But come early and socialize!

September 22, 2009 journal club

And we're off! We will meet Tuesday, Sept. 22 at 12:30 in Room W2303 in the School of Public Health.

Matt Beattie from the Zirkin lab will be presenting:

Zona Occludens-2 Is Critical for Blood-Testis Barrier Integrity and Male Fertility
Xu et al., Mol. Biol. Cell
published as MBC in Press, 10.1091/mbc.E08-12-1236 on August 19, 2009

This isn't really related to Matt's thesis project, but heck, the blood-testis barrier is cool.

Tentative schedule for fall 2009!

Room reservation is still pending -- but here's a "save the date" notice for the following Tuesdays at 12:30 ...

Sept. 22 - Matt Beattie (Zirkin lab)
Oct. 6 - TBD
Oct. 20 - Rachel Stine (Matunis lab)
[paper to be presented Lange et al., 2009, Cell, 138:855]
Nov. 3 - Becca Sheng (Matunis lab)
Nov. 17 - TBD
Dec. 1 - TBD
Dec. 15 - TBD

(And thanks to Matt, Rachel, and Becca for volunteering to go early and help get things rolling!)

Getting set for fall kick-off

I'm in the process of recruiting/arm-twisting for presentations for September and beyond. If you are willing and able [please!], do contact me --> jpevans@jhsph.edu

Also, please join me in welcoming the lab of Daniela Drummond-Barbosa to our group!

We are planning to continue with every other Tuesday at 12:30 for our meetings, for the time being at least -- although we might to some re-adjusting as the year goes on, to accommodate different schedules, to include some additional labs, etc.

May 26 journal club

After a few postponements, Matt Beattie from the Zirkin lab will present on May 26 (!).
He will have a hard act to follow, after Chris added some zip to his April 14 presentation with highlights of Han Solo being frozen (and how about a few bonus points for the wookie imitator?) ... but Matt works on the aging male, so at least that has Harrison Ford as a common theme.

Matt will present:

Evidence that age-related changes in p38 MAP kinase contribute to the decreased steroid production by the adrenocortical cells from old rats, Aging Cell 7:168

Oxidative stress-induced inhibition of adrenal steroidogenesis requires participation of p38 mitogen-activated protein kinase signaling pathway, Journal of Endocrinology 198:193

April 14 journal club

NOTE: We will be back in Room W2303 on April 14.
Chris from the Matunis lab will be leading a discussion of:

Plzf is required in adult male germ cells for stem cell self-renewal (Buass et al., Nature Genetics, 2004)

and a bit on the follow-up paper:
Histone lysine trimethylation exhibits a distinct perinuclear distribution in in Plzf-expressing spermatogonia (Payne and Braun, Dev. Biol. 2006)

Why these? ... Chris says:
"I chose this paper because it is one of very few reports that I am aware of demonstrating the role of an epigenetic regulator in the maintenance of mammalian germline stem cells. Although much work has been done regarding epigenetic modifications in differentiated germ cells, less is known about the role of epigenetic and chromatin modification in germline stem cell function. In our lab I am study the role of a chromatin remodeling complex, NURF, in the maintenance of Drosophila testis stem cells. Specifically, we are interested in understanding how chromatin remodeling factors contribute to the maintenance of stem cells within their endogenous niche including the role of the epigenetic state of a stem cell in its ability to interpret niche signals."

March 17 (St. Patrick's Day) journal club

Note: This meeting will be in W2015, one of the small classrooms on the SPH 2nd floor facing Wolfe St.

Melanie from the Matunis lab will be presenting:

Kanatsu-Shinohara et al., Homing of Mouse Spermatogonial Stem Cells to Germline Niche Depends on β1-Integrin
Cell Stem Cell, 3:533-542 (November 6, 2008)

Here is her comment on this paper:
"A key characteristic of stem cells is their ability to migrate back to and repopulate their niches. For example, following male germ cell transplantation in mice, infertile testes quickly regain spermatogenesis. This paper shows how spermatogonial stem cells (SSCs) home back into and migrate into the niche in a β1-integrin-dependent manner where they reinitiate and maintain spermatogenesis.

This paper is relevant to our work because stem cell adhesion to a niche is a universal feature of stem cells and because we find that integrin plays a role in the coordinate regulation of the two known stem cell types in the Drosophila spermatogonial niche: the germline stem cells (GSCs) and cyst progenitor cells (CPCs), which both require cell autonomous JAK/STAT pathway activation for their maintenance."

March 3 journal club

Matt from the Evans lab will be presenting. This is the plug he gave me (is it just me, or does this sound like one of the guys who writes the weekly plugs for the JHSPH happy hour?) --

"For this week I'm actually going to present a combination of two papers. Now, before you get irritated that you have to read two papers, hear me out. First off, they aren't too long. And secondly, they are really good and important papers:

The immunoglobulin superfamily protein Izumo is required for sperm to fuse with eggs (Nature, 2005)

Putative sperm fusion protein IZUMO and the role of N-glycosylation (BBRC, 2008)

Both papers were published by Masaru Okabe's group at the Genome Information Research Center at Osaka University. The main paper I'm presenting was published in Nature back in 2005, and was really influential because it gave new insight into the mechanism of sperm-egg fusion (Nature 434:234). The paper identified an IgSF family member, Izumo, as the first and only sperm protein to date shown to be completely essential for sperm-egg fusion. The second paper I will be discussing is a follow up paper published in October 2008. This paper explored the role that a conserved N-glycolsylation site played in Izumo function (BBRC 377:910). Despite the fact that Izumo is by far the most interesting molecular candidate on the sperm to mediate sperm-egg fusion, we still don't know much about how it functions. Therefore, I'll be discussing some of my work that focuses on the role that tyrosine O-sulfation, an understudied post-translational modification, may play in Izumo function.

Hopefully, you all will find the story as interesting as I do. I'll also go into the interesting history behind where Izumo got its name, how it was identified after sitting in a freezer for over 10 years, and some of the work that has gone into trying to make a vaccine using Izumo as the antigen.

Definitely take a look at the first paper from 2005, and if you have time, look over the second."

Feb. 17 journal club

Mouse differentiating spermatogonia can generate germinal stem cells in vivo
Barroca et al., Nature Cell Biology 11, 190 - 196 (2008)

Becca from the Matunis lab will be presenting. Here's what she says about the paper:

"Basically I chose this paper because it demonstrates that differentiating spermatogonia have the potential to reconstitute spermatogensis in gamma-irradiated mouse testes. It suggests that in the permissive microenvironment and with the appropriate cellular factors, differentiating spermatogonia can be re-programmed into germline stem cells.

This paper is directly relevant to my research as I am trying to understand the mechanism of dedifferentiation using Drosophila spermatogensis as a model system. Our system is especially useful because we know the precise location of the stem cell niche and have cellular markers that distinguish germline stem cells from their immediate daughters. We are also able to genetically manipulate the niche, and recently, we have developed methods to image the niche live in order to observe the cellular rearrangements that occur during dedifferentiation."

Feb. 3 journal club

For our upcoming meeting on Feb. 3, Erin from the Zirkin lab will be presenting a tale on Leydig cells. The paper is:

Tang et al., Notch signaling maintains Leydig cell progenitor cells in the mouse testis

... which is recent work from Blanche Capel's lab on Notch signaling and fetal Leydig cells. Erin works on Leydig stem cells in the adult (with a bonus focus on how these are affected by aging), and she'll use this paper to highlight some differences -- or at least to remind us that the assumption cannot be made that fetal and adult Leydig cells are the exact same beasts!

See you Tuesday at 12:30 in E2133 (remember that we are in a different room from where we usually meet for the next three meetings).

Enjoy Inauguration Day (Jan. 20 presentation moved)

So that you can tune in to watch or listen to the events of the presidential inauguration on Jan. 20, we will move that day's journal club.

Bill Wright will be doing his journal club presentation on May 12.