MD/PhD Wannabe's Research

[MeGrowTall]

Hello everyone. This is my first post here, but I have been reading the forums for a couple weeks now. To me, I feel as if training to become an academic physician is a calling, and I can't see myself being happy doing anything else right now.

Anyway, I was just wondering about the research experiences of all you other hopefulls. I have worked in a Drosophila lab for almost 4 years now, doing research on a transcription factor involved in axon guidance and helping to identify and characterize an epithelial sodium channel involved in thermosensation at a normal physiological temperature (the only one of its kind found as of now). I have used a wide variety of techniques ranging from site directed mutagenesis to RNAi. It really has been a fantastic exprience. I also did a research project in a human genetics lab that works on identifying the genetic basis of cleft lip/cleft palatte. This project was a bit more straight-forward. Just PCRs, gels, and sequencing to look for polymorphisms in a group of ~30 genes. Everyone share! I am always interested in learning more about current research.

I just took the MCAT on the 20th, and I am going to be applying in the fall. I am graduating in May, and I am planning to take a year off since I am poor. I'm thinking of getting a job at a lab in U of Chicago since it is one of my top choices for MSTP. Any advice about that? Any hints on what I can do to turn this off year into an advantage on an application?

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[dl2dp2]

I'm an undergrad at UC. YOu might want to consider contacting professors directly. They often have jobs.

 

[Original]

Wow your research sounds interesting! Seems like you can communicate it quite well too. That's going to help a ton at your interviews. It will also help you get interviews if you reflect it in your essays.

I worked on GABA transporters. We were trying to figure out the mechanism of its PKC-dependent regulation. To do this we studied the transport rates using tritium-labelled GABA for uptake assays in mamalian cells and oocytes(electrophys). To study the actual pathway of the transporter protein itself, we made a green fluorescent protein construct (GAT-GFP) which we confocally tracked in real time. Colocalization with the transferrin receptor (well known to be internalized via a clathirin/dynamin dependent mech and then recycled via an endosomal pathway), coupled with other confocal images sort of suggested that the GABA transporter was part recycled, part lysosomally destroyed. But who really knows .

I actually started out working on nicotinic Ach receptors. Mostly on the rig trying to figure out the ion stochiometry and mech of regulation. I found this freaking boring so I switched to GABA (the good stuff ). I also did reasearch in math. Trying to figure out the significance and uniqueness (or not) of the eigen-space of a math model of glycolysis. The math project was my honors (fast-track) thesis.

 

[xanthines]

check out the school at which I'm currently working, Emory University. There are 27 open positions for entry-level lab techs (or "Research Specialists" as they call them).

Your intestines have the surface area of a tennis court in order to allow for maximum nutrient absorption. It's amazingly good at bringing in nutrients and not bad things like bacteria. In some diseases such as ulcerative colitis and Chron's disease, ulcers and increased permeability to "bad stuff" causes chronic inflammation. It appears the tight junctions of intestinal epithelia become "leaky" but we have no idea through what mechanism these diseases occur. In fact, the mechanism of normal paracellular permeability isn't well known, as the identification of 2 novel proteins in just the past few months have shown. My lab is trying to work out the molecular structure of tight junctions in intestinal epithelia through bait peptide experiments, analytic centrifugation, and circular dichroism spectroscopy to name few (we also do the standard western blots and other less sexy techniques, which are of course just as important). So far we've come up with a lot of maybe's, theories, and guesses. I also have a side project which I'd like to give more time (as it's my very very own! <img border="0" alt="[Lovey]" title="" src="graemlins/lovey.gif" /> ) in which I'm investigating the possible effects of a diabetic drug (Avandia) for colon cancer. Avandia is a highly specific ligand for PPAR-y receptors which are highly expressed in the tissue culture cell line CaCo-2 (cancerous colon cells). I could go on and on...

... but my stomach is telling to fill it up.

Go Atl Braves!

-X

 

[Sonya]

Hi,

I'm an underad at WashU (well, graduating in about a week), majoring Biomed eng.

I have been doing research since I started here at Washu, which is for three years.

Basically, what I am doing is developing techniques to measure the force growing axons put on the surface they are growing on.

So, basically, this means designing new experiments to measure the elasticity of the surface we grow cells on (it's an acrylamide gel). I didn't learn that many standard techniques (except using a microscope and micromanipulator). But, it's a lot of reading articles, and then taking their method, making changes to fit our needs, and praying it works. and then altering it however we need to make it more accurate or more useful.

Measuring the forces axons put in development allows us to study localization and function of different motor proteins in the growth cone.

It's always been a challenge to be the most engineering/physical sciece oriented person in the lab. Especially since i'm not that engineering oriented. but my PI is even less.
I had myself second author in a publication in J. Neurosci.

I will be working in research for two years after graduation. I considered UChicago, and could've gotten a position there. but I have chosen to go to Northwestern instead.

Just look through the research going on at U Chicago, and e-mail professors whose work is interesting to you. They also have tons of openings listed in their page.
I know, the U Chicago webpage is soooo disorganized and it's a real pain to find a list of profs and their research. you need to scroll through all departments. Also, when you meet one, and maybe they don't need someone, or it wont work with them, don't be shy to ask to recomend another PI that may be a match for you.

Hope this helps.
Sonya

 

[JJ4]

Sonya -- you're going to do a PhD or MSTP??

Your research sounds pretty cool. I myself have my primary background in neural cell adhesion molecules. I have wanted to look at the novel mechanical properties caused by mutations of modular CNS proteins using atomic force microscopy but because my MSTP thesis research will not be in this area I have decided to hold off on it (for now anyway).

I had investigated a particular extracellular mutation in the L1 cell adhesion molecule and am very interested to look at mechanical stress responses of this as well (will be coming out in J. Neurobiol in June).

Too many interests -- so little time.

But biophysics of axon guidance -- GREAT STUFF!

 

[brandonite]

Hey, welcome to SDN!

There are usually a fair number of research jobs available. I actually think that the NIH has a program to hire people who have just graduated from an undergrad degree, and have them work on a project at the NIH. That would be a great experience. Ask RNAgirl about that one.

In general, at least as far as I've seen, there's not a shortage of positions out there. And these people here will know far more about the situation in the US than I will.

To date, my research has been in astronomy, actually. More specifically, developing high quality spectra (signal to noise in the thousands, as opposed to mere hundreds conventionally) of very bright, young stars. I have been more in the techincal/computer side of things. This summer and over next year, I will be working in imaging, so I'm hoping a lot of the tools that I've learned in stellar imagaing will transfer to biophysics. After next year, I'm not sure. I would like to get away from the techincal. I've actually given some thought to abandoning biophysics all together for some sort of biochemistry-oriented research.

Anyway, good luck!

 

[Sonya]

•••quote:•••Originally posted by JJ4:
•Sonya -- you're going to do a PhD or MSTP??

Your research sounds pretty cool. I myself have my primary background in neural cell adhesion molecules. I have wanted to look at the novel mechanical properties caused by mutations of modular CNS proteins using atomic force microscopy but because my MSTP thesis research will not be in this area I have decided to hold off on it (for now anyway).

I had investigated a particular extracellular mutation in the L1 cell adhesion molecule and am very interested to look at mechanical stress responses of this as well (will be coming out in J. Neurobiol in June).

Too many interests -- so little time.

But biophysics of axon guidance -- GREAT STUFF! •••••Hi.

wow, great. I didn't go into much detail b/c i thought i'd confuse everyone here. It's not exaclty biophysics.
Will write more after i finish finals. (wish me good luck here.... 5 more days of school for a long time... wish me the ability to live for 5 more days).

I'm an undergrad now. Will be doing research for two years, and then starting a MD or MD PhD programs. I'm definetly interested in academic medcine, so the PhD will be useful. But, i have these two years after graduation to give that more consideration.

JJ4, here the citation (for the article i published), if you're interested in axonal guidance.

Bridgman PC, Dave S, Asnes CF, Tullio AN, Adelstein RS.
Myosin IIB is required for growth cone motility.
J Neurosci. 2001 Aug 15;21(16):6159-69.
PMID: 11487639 [PubMed - indexed for MEDLINE]

Sonya

 

[JJ4]

Very cool...I'll check it out

Good luck on finals too

 

[MeGrowTall]

Original: Real time tracking of endocytosed vesicles? That is really cool!
Sonya: I want to read your paper as soon as I finish with my Immunology test this afternoon. SDN makes a good study break.

Y'all are a smart group, so I'll join in and go into a bit more depth on my research.
For the axon guidance, the transcription factor I am studying is called acj6 (human homologue is Brn3), and mutants result in flies defective in motility, sight, and olfaction. The protein has probably 4 isoforms so I am trying to determine if these isoforms are expressed in different cells. That would lend evidence to the idea that they have different functions. Now for the fun part - to do this I created transgenic flies that have either a DsRed fluorescent protein or a myc epitope tag protein fused to the 3' end of the gene. I also introduced several different sets of specific frameshift mutations in the exons involved in the alternative splicing so that the fusion protein I added will only be in frame if the acj6 was spliced a certain way. So, in a couple weeks I will finally be able see if my lengthy cloning payed off by doing some immunohistochemistry to determine the expression patterns of these isoforms. Whoo! Can't wait!

I also made an RNAi construct specific for the gene ppk in flies that we have recently determined is involved in thermosensation. How we assay for thermodefective flies is actually pretty cool. We establish a thermal gradient (18 C on one side, 33 C on the other) on an agarose gel and place a bunch of fly larvae of one genotype in the middle of the gel. After 10 minutes, we see how many larvae are on the hot side, and how many are on the cooler side. For normal larvae, about 95% of them are on the cool side - they just don't like that hot side. For some of our ppk mutants, including my RNAi transgenics, the percent on the cooler side is consistently lower, usually around 65-70%. We just recently have done some rescue experiments by reintroducing a wild type ppk gene back into our mutants, and it got the percent on the cool side back up to 90-95%. This is really exciting and we are putting the data together for a really nice manuscript. It's always fun when my PI gives a talk. He shows this video we have of little Drosophila maggots crawling around on agarose with red food coloring added.
Whew, if you read all that without getting bored, good job.

Thanks for the input on the jobs guys!

 

[Detroit Mick]

Sounds like there's a lot of good work going on out there. Congrats to you all.

I am currently working with a Thrombin Preconditioning (TPC) Model. TPC is a protective mechanism observed in laboratory animals. It results from inducing a small intracerebral hemorrhage (ICH) in rats and letting them recover for one week. After the recovery week, a larger ICH is induced and rats appear to be protected from the effects. Protection is observed through a decrease in edema in the brain and through various behavioral observational assays. ICH are induced using isolated rat thrombin (1-unit for small ICH & 5-units for large ICH) which is infusion directly into the right caudate nucleus.

Previous work in the lab has been able to demonstrate the up-regulation of two heat shock proteins (HSP27 & HSP32) during the 1-week period between the small & large ICHs. Also, work in the lab has shown that neuronal death appears to occur via an apoptotic mechanism. I have been be to shown a possible up-regulation of Fibroblast Growth Factor (FGF) using a new protein mass spectrometry technique known as SELDI (Surface Enhanced Laser Desorption/Ionization). Work outside my lab has shown the FGF may provide protection against an ischemic stroke and apoptotic neuronal death. I plan on spending the summer running some Western Blot and immunohistochemistry techniques to confirm my initial results and correlate the finding from our lab and to those outside findings.

The overall significance to to either develop a possible treatment for patients suffering a ICH or ischemic stroke or discover a possible biomarker for leaking blood vessels that may result in an ICH stroke.

I would also be interested in investigating mechanisms behind diabetic neuropathy.

 

[marq_bme]

What a fantastic thread! I'll be brief in describing my research..

Working in the biophysics dept. at the medical college of WI has given me huge insight into the collaboration between radiologists and engineers in using MRI technology

My current work involves the quantitative assessment of CBF (cerebral blood flow) and CBV (cerebral blood volume) in high grade gliomal cells. This is just a fancy way of saying that blood flow in tumor microvasculature may be interesting enough to look at! Using MRI, we can non-invasively assess blood volume in BOTH large and small capillaries. We are hoping to find some interesting results that will UNIQUELY allow us to determine whether post-operative tissue is recurring tumor or normal tissue--this will save the patient a TON of time in worrying after an operation as to whether he's going to be all right or not!

Keep the litany of responses coming!

 

[brandonite]

I heard about a really cool potential research topic yesterday. It might be something that I would be doing next year.

Basically, there is a biohazard level containment 4 (I think it is 4) facility in Winnipeg - the only one in Canada. So, the biophysics lab I am working for now has just developed a collaboration with them to work on using various types of imaging to detect infections diseases. For example, they are starting with variant CJD - mad cow disease in humans - and using head MRI to detect the prion changes in early stages.

I thought that sounded very cool...

 

[Street Philosopher]

I color brains.
The other thing I do is make surveys.

 

[Sonya]

Hi,

done with final. Done w/ college period!
miserable last semester... all time record low GPAs

anyway.

This is basically what i'm doing.

A growth cone puts force on the medium it grows on.

My job is to find the force it puts. My PI is using that to see what motor proteins are nessecary for growth (among many other things).

So when the neuron grows on acrylamide, it moves beads imbedded in the acrylamide. My job is to correlate movement of beads to force. So, we are using different methods of appyling a known force to the gel, and measuring the force produced.

(it's not nearly as simple a task as it sounds... remember all these are microscopic distances)

It's not really biophysics. The most physics level doesn't go much beyond freshman physics (hooke's law). I'm sure biophysics could make useful relevant contributions to it though.

JJ4,
was reading more of what you wrote. Yes, sounds very related to what we're doing (but i don't know that much of the bio of this). you're interstest seem very specific for being pre-med though (rather impressive actually).

This axonal guidance stuff isn't that interesting to me actually. When i started BME i thought i'd be interested in mechanics (that interest vanished), and neuroscience was intersting to. Thus, i ended up here.

My idea of really intersting now would be looking at electical changes as it relates to psych topic (drug addiction, learning and memory, etc). but, i'm intersted in this disease practical stuff, but really don't care for imaging.

I'll be doing reasearch at northwetern on mechanisms of pain (systems neuroscience) starting monday for the next two years.

BTW, I know this is sort of a sales pitch, but anyone in St. Louis area intersted in what I described above about axonal growth and looking for a lab position.. e-mail or PM me.

 

[Hopkins2010]

I'm going to be doing a rotation this summer in the Center for Image Guided Interventions at Hopkins.

Interestingly, some of the research there has a business connection. Elias Zerhouni, the new head of the NIH worked in close collaboration with my PI to develop microcoils for MRI and fMRI use in cardiovascular interventions. Zerhouni is one of the founders of Surgi-Vision, Inc. Needless to say, the Center has tons of money from both NIH and the company.

I plan to work on one particular application of interventional MRI, an MR scanning protocol and sequence design to be used in real-time angioplasty.

I'm also interested in exploring novel RF coil designs. This is a very different type of research, because it's very open-ended, ie inductive reasoning oriented. Instead of coming up with a coil shape a priori and going from there to the electromagnetic analysis, I want to develop a computer program that will look at optimal electromagnetic profiles for MRI and fMRI, and then use the results to "suggest" possible RF and gradient coil shapes.

sonic, have you moved to baltimore yet?

 

[atsai3]

MeGrowTall:

You should request (of your PI or the graduate student you report to) to be given the opportunity to do writing at every available opportunity. It need not be fancy -- eg., grant proposal, manuscript draft -- as long as it's _something_. For example, you could write a one-page memo summarizing the results of a series of experiments. Or something. In any case, anything you can do to get down on paper may prompt your employer/PI to provide you with more responsibility/opportunities.

Cheers
-a.

 

[exigente chica]

Last summer I did research at Colorado State University. I worked in a Biochem lab on determing the effects of free fatty acids on the insulin signaling pathway.
This year I work in a Nueroscience lab, I do my research on the Effects of Beta Amyloid and GFAP on glial cells.
Mostly tissue culture and western blots, but I love it!

 

[Bikini Princess]

Freshmen summer: Helped do PCRs etc for creating recombinant vaccine for IHNV (Infectious Hematopoetic Necrosis Virus). (Not human virus, a fish virus)

Sophomore summer: Plant pathology lab research on field microbes. (Playing outside sometimes)

Junior summer: Tried cloning up brand new protein involved in Xenopus oocyte maturation/translational regulation.

Senior year: Toxic effects of mercury on restriction enzymes.

New/Now: Regulation of ubiquitination process (Lots of IP's and 2hybrids with SCF complex)