Changing advisors, even disciplines, in graduate school

You’ve heard the old saying, “Don’t change horses in midstream.” But in graduate school, is that necessarily a bad thing?

Changing horses mid-game? Not so bad.

Changing horses mid-game? Not so bad.

Changing advisors part way through your graduate career can happen for several different reasons, but regardless of the cause, treat the change as an opportunity. Although you may initially think it is, it is not even remotely the end of the world. It is tempting to be influenced by external messages and think that there is a single right way to go about the journey of doctoral education, that there is no room for mistakes, and that you have to know exactly what you want to do from the beginning of your education. All three of these tropes are wrong.

I have changed research directions twice in my time as a graduate student, first changing from a Physics lab to a Biology lab to pursue more biological interests combined with physics, and then changing to a Biophysics lab when my advisor in biology left for a tenured position at a different institution. When I changed from a Biology to a Biophysics lab, skills in protein purification and NMR spectroscopy were transferable, but even in the extreme case that you change fields so drastically that nothing overlaps, just having previously gone through the process of learning techniques can make you better at it the next time. I think that these moves across disciplines and labs have improved my capacity to synthesize knowledge and skills, and to be adaptable.

Different unplanned circumstances, such as not getting into a certain lab, an advisor leaving the institution, or your interests and skills changing, may open an unexpected path that you can take with much happiness and productivity. I think it is unlikely that there is exactly and only one field or activity is right for a given person, and changing circumstances can be embraced as a way to pursue new or different interests. I applied to Hopkins excited to study astrophysics; I’m thrilled to now be making a career in protein science.

Dan Richman is a PhD candidate in Physics working in Bertrand Garcia-Moreno’s lab in the Department of Biophysics.

To flourish, stem cells need help from their friends

“Helper cells” improve survival rate of transplanted stem cells, mouse study finds

Like volunteers handing out cups of energy drinks to marathon runners, specially engineered “helper cells” transplanted along with stem cells can dole out growth factors to increase the stem cells’ endurance, at least briefly, Johns Hopkins researchers report. Their study, published in a recent issue of Experimental Neurology, is believed to be the first to test the helper-cell tactic, which they hope will someday help to overcome a major barrier to successful stem cell transplants.
Luminescent stem cells transplanted into mice alone (left) and with helper cells (right), shown one day after transplantation. Credit: Yajie Liang

Luminescent stem cells transplanted into mice alone (left) and with helper cells (right), shown one day after transplantation.
Credit: Yajie Liang

“One of the bottlenecks with stem cell therapy is the survival of cells once they’re put in the body — about 80 to 90 percent of them often appear to die,” says Jeff Bulte, Ph.D., a professor in the Johns Hopkins University School of Medicine’s Institute for Cell Engineering. “We discovered it helps to put the stem cells in with some buddies that give off growth factors.”

Stem cells can morph to take on any role in the body, making them theoretically useful to treat conditions ranging from type 1 diabetes (replacing insulin-producing cells in the pancreas) to heart disease (taking over for damaged heart cells). The biggest problem for transplanted stem cells, Bulte says, is that they’re initially grown in a dish with ready access to oxygen, then put in the body, where levels are relatively low. “They get a shock,” he says. Other research groups have had some success with acclimating cells to lower oxygen levels before transplantation; another promising strategy has been to provide the stem cells with scaffolds that give them structure and help integrate them with the host.

The research team, spearheaded by postdoctoral fellow Yajie Liang, Ph.D., wondered whether the cells’ survival could also be enhanced with steady doses of a compound called basic fibroblast growth factor (bFGF), an “energy drink” that spurs cells to grow. They engineered cultured human and mouse cells to make greater-than-normal amounts of bFGF under the control of a drug called doxycycline (dox). Making the bFGF gene responsive to dox meant the researchers could control how much bFGF was made, Liang explains.

The team then transplanted the engineered helper cells and stem cells into mice. The stem cells had themselves been engineered to make a luminescent protein, and using a special optical instrument, the researchers could monitor the intensity of the luminescence through the animals’ skin to see how many of the cells were still alive. The team gave the mice steady doses of dox to keep the bFGF flowing.

For the first three days after injection, the stem cells with helpers gave off a noticeably stronger signal than stem cells transplanted alone, Liang says, but a few days later, there was no difference between the two.

Despite the short duration of the helper cells’ effect, Bulte says, the experiment shows the potential of using helper cells in this way. Perhaps the ultimate solution to keeping transplanted stem cells alive will be to use helpers that give off a cocktail of growth factors, he suggests, as well as pre-conditioning for low oxygen conditions and scaffolds. “Once the rubber hits the road, it’s very important that the stem cells survive for a long time,” he says.

Other authors on the paper were Yajie Liang, Louise Ågren, Agatha Lyczek and Piotr Walczak, all of the Johns Hopkins University School of Medicine.

This study was funded by the National Institute of Neurological Disorders and Stroke (grant number 2RO1 NS045062) and the Anders Wall Foundation.

Konstantopoulos to present distinguished lecture on tumor cell migration

Biomedical Engineering 8 5 x 11 4-7Biomedical Engineering 8 5 x 11 4-7Biomedical Engineering 8 5 x 11 4-7Professor and Chair of the Department of Chemical and Biomolecular Engineering, Konstantinos Konstantopoulos will present a distinguished lecture for the Department of Biomedical Engineering on Monday, April 7 at 4 p.m. in the Mason Hall Auditorium on the Homewood campus of Johns Hopkins University.  His talk. “Joining Forces with Biology: A Bioengineering Perspective on Tumor Cell Migration,” will reveal some of his laboratory’s current findings on metastasis. The talk is free and open the Johns Hopkins University community. Refreshments follow the lecture.

Here’s the abstract of his talk:

“Understanding the mechanisms of cell migration is a fundamental question in cell, developmental and cancer biology. Unraveling key, physiologically relevant motility mechanisms is also crucial for developing technologies that can control, manipulate, promote or stop cell migration in vivo. Much of what we know about the mechanisms of cell migration stems from in vitro studies using two-dimensional (2D) surfaces. Cell locomotion in 2D is driven by cycles of actin protrusion, integrin-mediated adhesion and myosin-dependent contraction. A major pitfall of 2D assays is that they fail to account for the physical confinement that cells  encounter within the physiological tissue environment. The seminar will challenge the conventional wisdom regarding cell motility mechanisms, and show that migration through physically constricted spaces does not require beta1 integrin dependent adhesion or myosin contractility. Importantly, confined migration persists even when filamentous actin is disrupted. This seminar will also discuss a novel mechanism of confined cell migration based on an osmotic en

Johns Hopkins STEM students: can you speak Portuguese?

Amazonas_Brazilian_state-Amazon_rainforest-Americas-Brazil-Geography_of_South_America-Intact_forest_landscape-List_of_countries_by_forest_area-List_of_rivers_of_Amazonas_Brazilian_state-List_of_the_largest_country_subdivisions_by_area-NeotrThe Brazil Global Engineering Innovations Team is currently seeking a team member to participate in their project in Amazonas, Brazil. There is a particular need for a team member with Portuguese speaking and writing experience to help the team coordinate efforts with the local host group and assist the team in purchasing supplies and travelling while in Brazil. In addition to Portuguese speaking abilities, the team member should be self-motivated, a good team player and be interested in contributing to projects to benefit individuals in the developing economy of northern Brazil. Read more about INBT’s Global Engineering Innovation Program here. Interested students should contact Nathan Nicholes at nnicho12@jhu.edu by April 11.

Read more about the Global Engineering Innovations program here.

 

From bacterial intelligence to a cyber-war on cancer

Screen Shot 2014-03-18 at 11.40.42 AMINBT will host a special seminar, “From bacterial intelligence to a cyber-war on cancer,” on April 17 at 2 p.m. in Room 160 of the Mattin Center. The guest speaker is Eshel Ben-Jacob, PhD, professor and Maguy-Glass Chair in Physics of Complex Systems from Tel Aviv University. This event is free and open to the university community.

ABSTRACT: Cancer continues to elude us. Metastasis, relapse and drug resistance are all still poorly understood and clinically insuperable. Evidently, the prevailing paradigms need to be re-examined and out-of-the-box ideas ought to be explored. Drawing upon recent discoveries demonstrating the parallels between collective behaviors of bacteria and cancer, Dr. Ben-Jacob shall present a new picture of cancer as a society of smart communicating cells motivated by the realization of bacterial social intelligence. There is growing evidence that cancer cells, much like bacteria, rely on advanced communication, social networking and cooperation to grow, spread within the body, colonize new organs, relapse and develop drug resistance. Dr. Ben-Jacob shall address the role of communication, cooperation and decision-making in bacterial collective navigation, swarming logistics and colony development. This will lead to a new picture of cancer as a networked society of smart cells and to new understanding of the interplay between cancer and the immune system. Dr. Ben-Jacob shall reason that the new understanding calls for “a cyber-war” on cancer – the developments of drugs to target cancer communication and control.

Related Links:

Bacterial linguistic communication and social intelligence

Bacterial survival strategies suggest rethinking cancer cooperativity

 

 

CANCELLED: Spring mini-symposium features engineering, medicine

inbt-abstractCANCELLED: MINI-SYMPOSIUM TO BE RESCHEDULED. The Institute for NanoBioTechnology spring mini-symposium will be held March 17 from 8:30 a.m. to 12:15 pm. in the The Great Hall at Levering on the Johns Hopkins University Homewood campus. INBT sponsor’s these student run symposium’s twice a year to showcase the work of students from the institute, the Physical Sciences-Oncology Center, the Center of Cancer Nanotechnology Excellence and other affiliated laboratories. This event is free and open to the Hopkins Community. Refreshments provided.

Agenda

  • 8:30 -9:00  – Networking and breakfast
  • 9:00- 9:10 – Introduction
  • 9:10- 9:30 – “Probing cell traction forces in confined microenvironments” – Colin Paul, Konstantopoulos Lab
  • 9:30 – 9:50 – ” 3D tumor growth dynamics inside extracellular matrix (ECM) components” – Angela Jimenez, Wirtz Lab
  • 9:50 – 10:10 – “Acrylated hyaluronic acid hydrogels to study cancer angiogenesis” – Tom Shen, Gerecht Lab
  • 10:10 – 10:20 – Coffee Break
  • 10:20 – 10:40 – Amanda Levy,  “Development of a 3D system for the study of astrocyte-endothelial interactions” Searson Lab
  • 10:40 – 11:00 – Kristen Kozielski, “Bioreducible nanoparticles for efficient and environmentally triggered siRNA delivery to primary human glioblastoma cells”, Green Lab
  • 11:00- 11:20 – “X-Ray-Visible Stem Cell Delivery for Cardiac Regenerative Therapy via Microfluidics-based Microencapsulation” – Charles Hu, Mao Lab
  • 11:20 – 12:10 – “Advancing Innovation and Convergence in Cancer Research” Deputy Director of the National Cancer Institute’s (NCI) Center for Strategic Scientific Initiatives (CSSI).- Dr. Jerry S.H. Lee
  • 12:10 – 12:15 – Final remarks

2014 BioNano summer institute to be held at University of Illinois

It’s like summer camp for nanobiotechnology.

nanobioinstituteuofiThe 2014 BioNano summer institute will be held at University of Illinois Urbana-Champaign, July 28 to August 8. Click on this link for a pdf flyer.

Come for two weeks of lectures and hands-on training in engineering, biological, and physical science laboratory techniques covering topics such as cancer nanotechnology, cell mechanics, cell biology, molecular biology, lab-on-a-chip, and NanoBio devices. The institute is accepting applications from advanced undergraduates, graduate students, post-docs, and faculty from engineering, physical sciences, and biological sciences who are interested in state-of-the-art interdisciplinary research at the intersection of engineering and biology.

Applications must be received by midnight on Friday, March 28, 2014. Find details and apply online at this link: nano.illinois.edu/summer-institute-2014.

Lectures come from California Institute of Technology, Georgia Institute of Technology, Harvard University, Massachusetts Institute of Technology, Northwestern University, Stanford University, University of California Berkeley, University of California Merced, University of Illinois at Urbana-Champaign, University of Kentucky, and industry. The cost is $1,500/selected participant and breakfast and lunch each weekday and dormitory housing is included from July 27-August 8. NOTE: Limited financial assistance may be available toward the registration fee. If you wish to attend and require financial help, please indicate your request on the application form.

 

Q & A with Peter Devreotes

Back when the Johns Hopkins Institute for NanoBioTechnology first formed, we had an executive committee with faculty members from every University division to help guide our early footsteps. One of those memebers was Peter Devreotes, professor of cell biology at the School of Medicine.

Peter Devreotes with postdoctoral fellow Huaqing Cai. (Photo: Marty Katz)

Peter Devreotes with postdoctoral fellow Huaqing Cai. (Photo: Marty Katz)

Over the years Devreotes has advised and mentored students from the high school to postdoctoral level who are associated with INBT in his laboratory. Here, we have a short question and answer with Devreotes, produced for the Institute for Basic Biomedical Sciences newsletter. We e get to know a little bit about this faculty member, his personal and research interests and what inspires him.

How did you decide to study science?

DEVREOTES: I never thought about anything else. My father taught me a lot of math and took me on nature walks. I developed this fascination with everything in nature and wanted to know how it worked—I still do. I was actually a physics major in college—didn’t take a single biology class-but I decided to do a Ph.D. in biophysics, at Johns Hopkins’ Homewood campus. I was immediately fascinated by the mechanics of cells.

Follow this link to read more from this interview.

 

Cancer spreads through ‘Rock’ and ‘Rho’

n low oxygen conditions, breast cancer cells form structures that facilitate movement, such as filaments that allow the cell to contract (green) and cellular ‘hands’ that grab surfaces to pull the cell along (red). Credit: Daniele Gilkes

In low oxygen conditions, breast cancer cells form structures that facilitate movement, such as filaments that allow the cell to contract (green) and cellular ‘hands’ that grab surfaces to pull the cell along (red).
Credit: Daniele Gilkes

ROCK1 and RhoA genes found partly to blame for cancer metastasis. Gregg Semenza, co-director of the Johns Hopkins Physical Sciences-Oncology Center (PS-OC), led a team that made the discovery. The following comes from a Johns Hopkins press release:

Biologists at The Johns Hopkins University have discovered that low oxygen conditions, which often persist inside tumors, are sufficient to initiate a molecular chain of events that transforms breast cancer cells from being rigid and stationary to mobile and invasive. Their evidence, published online in Proceedings of the National Academy of Sciences on Dec. 9, underlines the importance of hypoxia-inducible factors in promoting breast cancer metastasis.

“High levels of RhoA and ROCK1 were known to worsen outcomes for breast cancer patients by endowing cancer cells with the ability to move, but the trigger for their production was a mystery,” says Gregg Semenza, M.D., Ph.D., the C. Michael Armstrong Professor of Medicine at the Johns Hopkins University School of Medicine and senior author of the article. “We now know that the production of these proteins increases dramatically when breast cancer cells are exposed to low oxygen conditions.”

To move, cancer cells must make many changes to their internal structures, Semenza says. Thin, parallel filaments form throughout the cells, allowing them to contract and cellular “hands” arise, allowing cells to “grab” external surfaces to pull themselves along. The proteins RhoA and ROCK1 are known to be central to the formation of these structures.

Moreover, the genes that code for RhoA and ROCK1 were known to be turned on at high levels in human cells from metastatic breast cancers. In a few cases, those increased levels could be traced back to a genetic error in a protein that controls them, but not in most. This activity, said Semenza, led him and his team to search for another cause for their high levels.

What the study showed is that low oxygen conditions, which are frequently present in breast cancers, serve as the trigger to increase the production of RhoA and ROCK1 through the action of hypoxia-inducible factors.

“As tumor cells multiply, the interior of the tumor begins to run out of oxygen because it isn’t being fed by blood vessels,” explains Semenza. “The lack of oxygen activates the hypoxia-inducible factors, which are master control proteins that switch on many genes that help cells adapt to the scarcity of oxygen.” He explains that, while these responses are essential for life, hypoxia-inducible factors also turn on genes that help cancer cells escape from the oxygen-starved tumor by invading blood vessels, through which they spread to other parts of the body.

Daniele Gilkes, Ph.D., a postdoctoral fellow at the PS-OC and lead author of the report, analyzed human metastatic breast cancer cells grown in low oxygen conditions in the laboratory. She found that the cells were much more mobile in the presence of low levels of oxygen than at physiologically normal levels. They had three times as many filaments and many more “hands” per cell. When the hypoxia-inducible factor protein levels were knocked down, though, the tumor cells hardly moved at all. The numbers of filaments and “hands” in the cells and their ability to contract were also decreased.

When Gilkes measured the levels of the RhoA and ROCK1 proteins, she saw a big increase in the levels of both proteins in cells grown in low oxygen. When the breast cancer cells were modified to knock down the amount of hypoxia-inducible factors, however, the levels of RhoA and ROCK1 were decreased, indicating a direct relationship between the two sets of proteins. Further experiments confirmed that hypoxia-inducible factors actually bind to the RhoA and ROCK1 genes to turn them on.

The team then took advantage of a database that allowed them to ask whether having RhoA and ROCK1 genes turned on in breast cancer cells affected patient survival. They found that women with high levels of RhoA or ROCK1, and especially those women with high levels of both, were much more likely to die of breast cancer than those with low levels.

“We have successfully decreased the mobility of breast cancer cells in the lab by using genetic tricks to knock the hypoxia-inducible factors down,” says Gilkes. “Now that we understand the mechanism at play, we hope that clinical trials will be performed to test whether drugs that inhibit hypoxia-inducible factors will have the double effect of blocking production of RhoA and ROCK1 and preventing metastases in women with breast cancer.”

Other authors of the report include Lisha Xiang, Sun Joo Lee, Pallavi Chaturvedi, Maimon Hubbi and Denis Wirtz of the Johns Hopkins University School of Medicine.

This work was supported by grants from the National Cancer Institute (U54-CA143868), the Johns Hopkins Institute for Cell Engineering, the American Cancer Society and the Susan G. Komen Breast Cancer Foundation.

TO BE RESCHEDULED: Shashi Murthy of Northeastern University

THIS SEMINAR HAS BEEN CANCELLED DUE TO THE THREAT OF A WINTER STORM AND WILL BE RESCHEDULED.

“Ever heard about seaweed, Mucinex®, stem cells, and the International Space Station in the same conversation?” is the name of the talk to be given by Johns Hopkins University alumni Shashi Murthy, PhD, at 10:30 am on Thursday, February 13 in the Shriver Hall Clipper Room.  The talk is free and open to the Hopkins community and sponsored by Johns Hopkins Institute for NanoBioTechnology.

Shashi Murthy

Shashi Murthy

Shashi Murthy is an associate professor in the Department of Chemical Engineering and Founding Director of the  Michael J. and Ann Sherman Center for Engineering Entrepreneurship Education at Northeastern University. This presentation will combine a scientific description of a methodology for stem cell purification designed in by the Murthy laboratory with the story of its ongoing commercialization.  Murthy will also talk about how the vision behind the Michael J. and Ann Sherman Center for Entrepreneurship Education came into being and how this Center is impacting the undergraduate experience in the College of Engineering at Northeastern University.