Grants and what we'll do with them

We’ve been incredibly fortunate lately. Our lab has received two grants which will help fund us for the next five years. Grants help to fund our science by paying the salaries of the people in our labs. The majority of a grant is salary support, unless it’s been otherwise designated. Grant money supports the livelihood of people working in the lab. Here is a quick summary of some of the work that these to grants will support:

NIH/NIGMS MIRA R35 - Investigating the Impact of Genetic Variation on ER Stress Response and Disease

This grant differs from the standard NIH R01 in that it is meant to fund multiple projects that fall under a common theme in a particular lab. For us, this was really nice, as we have common thread of understanding how genetic variation impacts disease. This grant will support three projects:

Project 1: Understanding the underlying genetic architecture that contribute to differences in individual ER stress responses.
Project 2: Understanding how genetic variation affects Retinitis Pigmentosa, a retinal degeneration disease.
Project 3: Understanding how genetic variation affects NGLY1 deficiency, a rare metabolic disorder of deglycosylation.

You can read a more formal summary of this grant here.

Glenn Award for Research in Biological Mechanisms of Aging

Again, our lab is broadly interested in understanding how genetic variation impacts the ER stress response. This grant will allow us to begin studies where we introduce a new dimension to this work – age. We are interested in understanding how the role genetic variation on the ER stress response changes as an individual ages. This has important implications for age related diseases like cancer and dementia.

These grants will go a long way in advancing the work in our lab. We have a talented team of excited techs, students, and postdocs working hard on these projects.

Science is for everyone.

Science is a human pursuit. Science should be a safe space. Science is for everyone.

Recent political developments have put everyone on edge. 

No matter how you feel, or how you voted, or how you identify, you should be welcomed into this grand pursuit we call science. 

People should feel safe in the lab and in the field. 

In my lab, you will be welcomed and you will feel safe. I will be your mentor and ally. I will support you and advocate for you.

I will not tolerate harassment.

You can come to me and I will listen. 

We can make science an example for our society.

The Chow Lab is heading to ASHG

The Chow Lab is heading to ASHG this coming week. Here’s what we’re doing at the meeting:

Thursday 11:30 in room 302 - PgmNr 183: "Diet rescues lethality in a model of NGLY1 deficiency, a rare deglycosylation disorder."
-    Clement will be discussing this exciting new project in the lab. Come hear about how we use model organisms to learn about rare diseases.

Clement will be co-moderating a session on Saturday morning at 10:15 in room 119: “Session #84: Novel Discoveries in Mendelian Disease”
-    This will be great. Come hear about recent advances and new discoveries related to Mendelian disease.

Josh Lowry, one of our postdocs, is attending as a first timer to ASHG! If you see him, say hi!

And…We are looking for people interested in working on rare disease. If you’re interested, find Clement or contact him

Summer wrap up.

Summer is always too short. But we managed to still get a lot done. I'm very proud of the lab! The lab is growing and I’m excited that our team is made up of people with diverse experiences and backgrounds.

Some highlights:

  • It was very exciting to have Shani join our lab this summer. Shani is an undergrad at UCLA and she has made some incredible progress on our retinits pigmentosa project.
  • Josh and Becky joined this summer as postdocs. They have both hit the ground running and are moving forward quickly.
  • We attended GSA’s TAGC meeting in Orlando.
  • We celebrated new lab members with lab lunch.
  • We celebrated birthdays with donuts.

That’s a lot!

We wrapped up the summer with a lab dinner together.

Clement, Shani, Elaine, Josh, Demi, Katie, becky

Clement, Shani, Elaine, Josh, Demi, Katie, becky

We’re so excited to see what this year brings!

 

 

The Chow Lab heads to TAGC16

I will be heading to GSA’s The Allied Genetics Conference next week in Orlando (AKA TAGC16). It’s unique in that, for the first time, GSA is attempting to bring together all the model organism genetics under one roof. THERE WILL BE A LOT OF SCIENCE! 

This is especially exciting for the Chow Lab because this will be the first national meeting where we present our own science. Our work spans multiple model organisms and crosses functional and quantitative barriers. This made TAGC16 especially exciting for us, but also like Sophie’s Choice, trying to decide which project to present. Rather than choosing, we submitted two abstracts!

Our mouse project was chosen for a talk. We have been investigating the effects of ER stress on the placenta. We are using RNAseq and small RNAseq to explore how ER stress reorganizes transcriptional networks in the placenta. I will be giving the talk during the Mouse Development session on Thursday from 4-6PM. Talk M272

Our fly project was chosen for a poster. We have been exploring the pathogenesis underlying lethality in a Drosophila model of NGLY1 deficiency. This is mostly the work of our tech, Katie Owings. It’s turning out to be a really interesting story! Please drop by and check it out. Poster D1331

I also contributed to a talk and a poster from my postdoc with Andy Clark and Mariana Wolfner
1.    D121: Investigating the female’s role in sperm competition in Drosophila melanogaster.
2.    D1408: Male genotype-specific transcriptional responses to mating in female Drosophila melanogaster.

I will also be moderating the "Comparative Genomics, Computational Methods and Evolution" session on Thursday morning with Steve Munger

Finally, I am particularly excited to be a mentor at the “Mentoring Roundtables” event on Thursday from 12:30-1:30. I will be at the “Transition to Independence” table. Come hear about what has worked for me (so far) in my transition.

I hope you find me and say “hi”, but more importantly, I hope you’ll look for our science and give us feedback!

On science communication

Science communication is an important part of a scientist’s job. It’s an opportunity to tell the public about how awesome and spectacular your work is. I recently recorded a podcast on The Scope about some of our work on genetic variation and disease. It was really fun. I was able to think about how to distil my science into just the essential non-jargony points.

Sometimes, however, science communication needs to just be the voice of reason. Sometimes you just have to tell a Cosmo reporter that a genetic test won’t help you find a romantic partner. Don’t ask. Just read this.

The lab is growing!

So much excite!

Two postdocs are joining the lab this summer and they are both bringing new skills and talents that will enrich the lab.

As a grad student, Josh Lowry used whole genome sequencing methods to map and identify new C. elegans mutants that affect syncytial membrane architecture in oogenesis (here). In our lab, he will be applying his computational skills to understanding the pathogenesis underlying NGLY1 deficiency. Josh is starting in June.

As a grad student, Becky Palu studied the role of Sir2 and HNF4 in Drosophila insulin signaling and metabolism (here). During her postdoc, she will be using her strong background in functional Drosophila genetics to understand the mechanisms underlying natural variation in Retinitis Pigmentosa. Becky is starting in August.

I am eager to see the lab hum with activity! 

 

What to expect

Whether it is for a career in academics, industry, policy or whatever, grad students and postdocs join labs for training. Working in an academic lab can provide valuable skills for all kinds of careers and I take this responsibility very seriously. Students and postdocs are here to learn, not just work.

I am a new professor. I don’t have a lot experience to draw on. But, I do know that I am successful because of the people that trained me.  Obviously, there isn’t a magic bullet for every trainee, but here are some general lessons I picked up along the way. I will try to implement these in my lab:

1)    GOALS: It’s important that everyone has goals – long term career coals and short term progress goals. I will make sure that we reassess and develop these goals on a regular basis. 

a.    CAREER: Whatever your career goals are, I will try my best to provide the necessary resources you need to reach those goals. If I don’t have the answer, we will find someone who does. 
b.    LAB: We will set project goal posts to shoot for. We will reassess on a regular basis and decide if the goals need to be reset or extended.

2)    WRITING: Nearly everyone is terrible at this when they start and nearly everyone improves with practice. So, I will push you to write. Write abstracts, posters and papers. You will write the first drafts. Then, we will work together to improve it. Rinse and repeat.

3)    SPEAKING: Just like writing, nearly everyone is terrible at first. Unlike writing, nerves are involved and the only way to get over the fear, is to practice. GIVE.LOTS.OF.TALKS. Again, I will push you to present. From the beginning you will be presenting for lab meeting. I will encourage you to volunteer for journal clubs, local talks and national meetings. We will always submit abstracts with talks in mind. PRACTICE putting together a talk and giving a talk.

4)    SUPPORT: My door will always be open. Come to me for support. If something is not working in lab, let’s figure it out together. If you feel you are missing something in your experience, let’s figure out how we can fix it. 

5)    CHALLENGES: Expect to be stretched and challenged intellectually. We have (a true) multidisciplinary research program and that means that projects may extend into realms that you aren’t comfortable with. I expect my trainees to leave my lab with a broad outlook on genetics. 

These are a few of the (many) ways I was mentored and helped me be successful (so far). I am still learning this PI thing and of course I will modify how I think about this as I gain experience. But, if you join us, you can expect that I will try my hardest to ensure that your experience will prepare you for your next step. 

Please chime in and let me know how I can be a supportive PI and mentor. What have I missed?

Why I do science

Human disease isn’t just a cell in a dish or a fly in a vial. This first became clear to me as an undergrad. I had the opportunity to intern at a perinatology clinic that dealt with high risk pregnancies. A large proportion of the cases they saw were due to genetic disease in the fetus or baby. I sat in on procedures and genetic counseling sessions. I saw firsthand what genetic disease does to a family. Pain, suffering and unending questions.

As basic scientists, we often forget this. We tell ourselves that we strive for knowledge and truth. This is true. But, our work has so much potential to provide answers and even transform lives. This is why I do science.

As a grad student I worked on Charcot Marie Tooth (CMT) disease, a severe peripheral neuropathy. This story began with a spontaneous mouse mutant, basic science. I cloned the gene and characterized the mouse. Based on this work, we thought it had a lot of similar neurodegenerative issues as patients with CMT. I screened a number of patients and found several families with mutations in the same gene. When this was reported back to the families, we received notes expressing relief that they hadn’t done something wrong to make their kids sick. Now, there is gene test and numerous other patients have been diagnosed. This is what basic science can do.

It’s important to remember the human face behind the disease. We recently began a project looking into the biology underlying NGLY1 deficiency. This is a disorder of deglycosylation and patients have developmental delay, movement disorders, and many other symptoms. I recently met the first identified patient with NGLY1 deficiency. This reminded me again, that NGLY1 deficiency is not a project. It’s a genetic disease with a human face and human suffering.

Not every experiment will lead to therapy. Not every experiment will improve humanity. But if one does, then we’ve succeeded. Behind all this biology is human disease. Behind the disease is a human face, human suffering. This is why I do science.

The importance of scientific societies

I was recently profiled as a new faculty member on the Genetics Society of America (GSA) website. For the profile, I was asked what role GSA played in my career. This got me thinking about the important role that scientific societies play in the development of all trainees. 

Travel awards and conference organization are two obvious ways that an organization like GSA might influence training. However, the potential is much greater and I think most scientific societies are untapped resources for trainees. As a graduate student, I joined the American Society of Human Genetics (ASHG) Training and Development Committee. This committee is tasked to help develop resources and programs for students and postdocs. After serving for a few years, I was asked to chair the committee. This was a great opportunity. I learned a lot about how the society functions and how decisions are made. I was able to network with leaders in the field. I was even asked to represent ASHG at a FASEB planning meeting. All this was invaluable experience. 

Most scientific societies work hard to provide trainees with the resources and opportunities they need to succeed. More and more, these societies are developing career resources beyond the typical academic route. The staff care deeply about trainee development. Dr. Michael Dougherty, Director of Education at ASHG, and Dr. Elizabeth Ruedi, Director of Education and Professional Development at GSA, are two stunning examples of society staff who work tirelessly to provide invaluable trainee resources. 

I encourage all trainees to take advantage of society opportunities to serve and lead. Reach out to your society. Don’t wait for an opportunity to come to you.

Mendelian diseases as quantitative traits

I recently gave a talk at the annual American Society of Human Genetics meeting in the Novel Genes, Novel Regulators, and Monogenic Diseases session. I was very pleased by the reception of my talk and of the main message I was trying to convey. I thought I would briefly rehash the main point: Mendelian diseases are not simple and should be viewed as quantitative traits.

I presented our work on identifying genetic modifiers of Retinitis Pigementosa (RP), a heritable form of retinal degeneration. We crossed a Drosophila model of RP onto ~200 wild-derived Drosophila strains. These strains contain genetic variation found in a wild population and were NOT mutagenized. When on different backgrounds, this Mendelian disease presented with a HUGE range of retinal degeneration. In short, the phenotype was quantitative. We went on to identify a list of novel candidate genes that make a lot of biological sense. We used natural genetic variation to show that this Mendelian disease is, in fact, complex.

This message may be obvious. After all, the push behind precision medicine is the fact that every individual is different and may present with slightly different disease outcomes and respond differently to therapies. However, when speaking to other scientists studying Mendelian diseases, genetic background and modifier genes are a pesky nuisance. I challenge everyone to embrace these effects.

In order to fully understand the phenotypic spectrum and genetic architecture of Mendelian diseases, we need to treat them as quantitative traits.

Our logo

You'll notice that our lab is represented by a pretty neat logo. I decided that I wanted a logo designed for the lab because I didn't want my face to be the lab brand. I want this lab to function as a team - I just happen to be the PI. 

Our logo has four symbols, a DNA helix, a human, a mouse and a fly. The DNA helix represents our central theme of harnessing the power of genetic variation to answer the questions we are chasing. The human symbolizes the fact that even if we are doing basic science, we strive to contribute to solving aspects of human disease and contributing to the development of therapies. The mouse and the fly show that we believe strongly in model organism research. Continuing advances in model organism biology make these tools more powerful than ever. We use both the mouse and the fly to study and model how genetic variation can impact human diseases. 

I am hoping that this logo will serve as a good reminder for us as we push forward.