LAMP

by Juliane

This is a lamp, lamps come in lots of different sizes and shapes. Some of them are even shaped like this:

The lysosome-associated membrane glycoprotein, Lamp to its friends, is part of the lysosome and therefore involved in digestion of foreign materials and autophagy. LAMP1 and 2 were first discovered in 1985, since then they have been widely studied and shown to be involved in quite a few important pathways in human cells.

Immune response: LAMP1 is necessary for delivery of perforin to lytic granules.

Cancer: LAMP 1 is a marker for melanoma metastasis into lymph nodes.

Apoptosis: LAMP1 and 2 promote apoptosis.

General Research: LAMP is a commonly used as a marker for lysosomes.

The scientists, who named this versatile protein, were either very boring (it describes exactly what it is) or very creative (there is beauty in simplicity).

References:

www.ikea.com
http://www.pathologyoutlines.com/topic/cdmarkerscd107.html
Chen JW et a. (1985) Identification of two lysosomal membrane glycoproteins. J Cell Biol. 1(1):85-95.
Krzewski K et al (2013) LAMP1/CD107a is required for efficient perforin delivery to lytic granules and NK-cell cytotoxicity. Blood. 121(23):4672-83.
Sato H. et al (2009) Altered expression of glycoproteins on the cell surface of Jurkat cells during etoposide-induced apoptosis: shedding and intracellular translocation of glycoproteins. Biochim Biophys Acta. 1790(10):1198-205.

Effects of remote, retroactive intercessory prayer

by Juliane

Effects of remote, retroactive intercessory prayer on outcomes in patients with bloodstream infection: randomized controlled trial. Published by Leibovici in the British Medical Journal BMJ in 2001. BMJ currently has an impact factor of 17.215.

The title of this article sounds kind of strange, so let’s see if I have got this right:

Remote prayer: praying to your deity of choice on behalf of a person you don’t know. There are quite a few websites on which you can submit a prayer request to a holy person or a group of people.

Retroactive: backwards through time, in this case praying for the health of people in the past.

Intercessory prayer: praying to your deity of choice on behalf of somebody else’s health, hoping that said deity will intervene in response to the prayer and speed up recovery of the sick person. Intercessory prayer is actually fairly well studied: there are 94 articles listed in Pubmed (8 of which are responses to the Leibovici paper); however most of them are published in fringe low impact journals. A Cochrane review did not recommend further clinical trials.

Bloodstream infections: Bacteria that spread into the blood of a patient

Randomized controlled study: “A study design that randomly assigns participants into an experimental group or a control group”

The author seemed to have studied the effects of remote prayer on blood stream infections backwards through time.

Let’s now have a look at the abstract: Typical for medical abstracts it is divided into objective, study design, results and conclusions. It confirms what the title promises, the author researched the effects of remote prayer backwards through time. The patients were hospitalized between 1990 and 1996, while the praying took place in 2000. The author measured mortality and length of stay in the hospital as his variables and concluded that the intervention group fared better on both counts. He therefore concludes that retrograde remote prayer works and should be considered as a useful tool for medical doctors.

Let’s examine how he reached this conclusion:

Introduction: here the author sets up the bold hypothesis that time might not be linear which he supports with this highly theoretical paper.

Methods: 3393 patients diagnosed with bloodstream infections in an intensive coronary care unit were randomly distributed into two groups. A list with the first names of one group was given to a (holy?) person who said a prayer for them. Then three variables, death, duration of hospital stay and duration of fever were compared. The null hypothesis, prayer works backwards through time was tested using a chi2 test or a Wilcoxon rank-sum test.

And now the most interesting part, the results. They are rather limited, the main findings are summarized in this table.

There is no significant difference in the duration of fever between the treatment groups, however the duration of hospitalization differs significantly between the two groups. The maximum stay in the control group was almost twice as long as the intervention group. While there are very few differences in the lower quartile the upper quartile differs (significantly?) between the two treatment groups. In conclusion, prayer for people backwards through time works.

The author states that the trial design is “flawless”, because of the “perfect blinding to patients and medical staff of allocation of patient allocation to the two groupss and even the existence of the trial”. He did not offer an explanation or hypothesis for this astonishing result.

Of course there are many problems with this paper, not in the least being the lack of informed consent of the participants and permission of an oversight committee at the hospital such as an IRB or ethical review committee. It appears that most of the significance of this study can be ascribed to one outlier in the control group, whose stay in the hospital was extended. However, without access to the raw data it is hard to prove this. The fact that the median does not differ between the two treatment groups is another hint, i.e. that the results might look very different when the outlier is removed.

This paper takes a ridiculous hypothesis and runs with it. It shows that to do good science we should not just discard a hypothesis, because it sounds too far fetched, but do our best to prove or disprove it. Leibovici did not do this. The experiment wasn’t very well designed, no matter what he claims and additional key information, such as what god was chosen to intervene following receipt of prayers are missing from the paper. The statistical tests the author chose to perform are not commonly used to test for differences in treatment groups during clinical trials, perhaps a T-test would have been more appropriate.

A better-designed experiment might have yielded a different result. However, it is important as scientists, to not just say “that’s stupid, so it can’t be true”, but to prove from the data presented that the conclusions reached are incorrect or point out flaws in the experimental design.

Naturally quite a few papers were published in response to this study, e.g. “You cannae break the laws of physics, Captain.”

This paper also sparked an interesting discussion on the BMJ website and is often cited by people, who believe in intercessory prayer and don’t have a scientific background. This shows that even with the best of intentions to write a light hearted scientific paper with a comedic edge can have a very real and sad backlash.

In conclusion, I like this paper, mainly because in the end they show a picture of a reindeer for some reason.

About being a scientist

by Francesca Seta

Francesca used to be a BUMC postdoc, recently she got a position as assistant Professor in the Department of Medicine at BUMC, where she researches the molecular and genetic mechanisms of arterial stiffness and how to cure and prevent it. She also wrote an interesting post for the postdoc blog, enjoy!

About being a scientist

The Danish toy giant LEGO has recently grabbed media attention for the release of a new minifigure:  the “scientist”. The little yellow brick wearing lab coat, glasses and a pen in the pocket looks cute and sharp; definitely not a mad, nerdy or evil scientist, as often portrayed in the collective imaginary (think Shelley’s Dr. Frankeinstein or Doc from the movie “Back to the Future”). Most of all, the “scientist” is female. As I dug deeper, I was surprised to discover that LEGO has been criticized in the past for gender bias and its previous attempts to market to girls found guilty of perpetuating the “pink and pretty” stereotypes of female representation. The new “lady scientist” may be, in part, an attempt to amend such gender bias accusations.

This came just a few months after yet another much debated release: the book “Lean in” from Sheryl Sandberg, Facebook COO, in which the author encourages women to engage more in leadership roles in the workplace and blames them for not embracing their full potential. All the debate about gender disparity in the American workforce and particularly in STEM careers (science, technology, engineering, mathematics) made me think: what does really take to succeed in science, independently if you are a guy or a girl? I asked myself this very question many years ago as a PhD (female) student when I was looking for sources of inspiration and directions about my future and my career. At that time, I came across a great book, “Advice for a young investigator” from the Spanish scientist Santiago Ramon y Cayal. According to the eminent neuroanatomist, hard work, passion for work, family and country, ambition, patience, humility, pursue of original data and master of the techniques are the qualities required to succeed in science. Most importantly, the idea of having to be exceptionally smart or genius, as sometimes scientists are envisioned in the popular perception, was not even mentioned in the book. Although the book was first published in 1897, the principles it promotes are timeless and universal and I reasoned that being successful in science boils down to willpower, self-motivation and perseverance, none of which, are gender-related qualities or restricted to STEM careers (a sport coach would probably have a similar piece of advice for young athletes as Ramon y Cayal had for young investigators).

In a recent trip to my home country, Italy, I went to renew my ID and the office clerk asked me what my profession was. To my surprise, the profession “scientist” was not in the list of choices although they had “academic researcher”, which is pretty close. Despite the profession of “the scientist”  being somehow nebulous and elusive in Italy, growing up I never felt discouraged to pursue a STEM education and career and definitely not because of my gender. Now, as an early stage investigator, I come to appreciate how lucky I was to have teachers, family and mentors that rewarded perseverance and valued resilience as I was growing up. Those are the very qualities that, during my PhD and postdoctoral years, helped me to face failed experiments, long hours in the lab and many years of training at low pay. And probably these are the very same qualities that keep us scientists going these days in face of NIH spending cuts and low grant success rates that threaten to shut down our labs. Sure, STEM careers are tough but after all, the ideal of making an impact against human suffering, advancing knowledge and the satisfaction that comes from successful experiments, new discoveries, published articles and funded grants, make it all worth it. Despite the hardship and the challenges, science is creative, exciting and rewarding if you do not give up. And hopefully the little “scientist” LEGO figure will help to pull more young people into it.

Top ten tips to identify the companies you want to work for

by Lauren, CEO of propel careers

this post is reposted from the propel careers blog.

Numerous options exist to identify potential companies to work for, especially those companies that are innovative, but not (yet) well-known. Below is a top ten list of ways to uncover exciting and innovative companies relevant to your area(s) of interest. The advice provided below is applicable to all industry sectors, but the specific examples have been tailored for the life sciences sector.

Tip 1: Utilize your connections

Your connections include college and graduate school classmates, lab mates, friends, clubs and social groups, connections from industry associations, neighbors, mentors, teachers, and people you meet at networking events and conferences. These connections should extend to alumni of your academic institutions. Even though you may not know these individuals personally, you share a common experience that can be leveraged for your career search. Your connections may not be involved in your exact area(s) of interest (i.e. cancer research or cardiovascular medical devices), but may have connections to those who are. Develop your elevator pitch/email and share it with your contacts to succinctly inform them of your background and what you are looking for (i.e. research in a small biotech or consulting in a boutique firm). Use LinkedIn to keep in touch. Build out your profile so that your connections and potential employers can see your background.

Tip 2: Industry News Feeds

Every industry has news sources that profile advances, industry trends and companies in the sector. Sources such as www.Xconomy.com (entrepreneurial technology/life sciences oriented companies), www.biospace.com (life sciences companies), or www.devicespace.com (medical device companies) are a few examples. Hundreds of news sources exist (from general to extremely specific), so seek out news feeds relevant to your interests and subscribe to them.

Tip 3: Publications

Search Google Scholar or Pubmed to identify research related to your interests. Recent publications in your area of interest can tell you a lot about who is currently working in the space.

Tip 4: Conferences

Conferences are ubiquitous in every industry. In the life sciences industry, there are large conferences such as BIO http://www.bio.org/ or AdvaMed http://advamed.org , disease focused conferences such as AACR http://www.aacr.org/ or Society for Neuroscience -http://www.sfn.org/ and smaller focused conferences such as 2nd Annual Predictive Preclinical Models in Oncology conference http://www.worldpharmacongress.com/Pre-Clinical-Models-Oncology/. Once you identify conferences relevant to your interests, look at the speakers, posters, and exhibitors. This will help uncover companies that work in your area and provide insight into organizations which may be a fit.

Tip 5: Industry Associations and Trade Groups

Organizations such as MassBio http://www.massbio.org/ and MassMedichttp://www.massmedic.com have a wealth of information on biomedical research companies in Massachusetts.s. Similar resources are available in most states, and most countries have organizations that represent and focus on specific industry sectors. These organizations are an invaluable resource. Sign up for their newsletters and newsfeeds to keep yourself current.

Tip 6: Industry Reports

Many consulting firms like Ernst and Young and PWC compile extensive industry sector specific reports or white papers. Their life sciences and medical technology reports are very informative and provide tremendous information about companies, trends, and issues related to the industry.

Tip 7: Venture Capital Organizations

Look into websites for venture capital organizations that fund companies in your area of interest, especially if you are looking to work in a start-up. Many of these organizations profile companies they have invested in on their websites. It is not uncommon for portfolio companies to initially operate in “stealth mode,” therefore it may be hard to find information about them from other sources.

Tip 8: LinkedIn

Search LinkedIn using the advanced search feature. In the keywords section, enter your areas of interest – i.e. prostate cancer therapeutics, oncology microfluidic diagnostic platform, or atrial fibrillation. Search by 1st degree connection and see what comes up. If only a few people appear in the search results, then expand the search criteria to 2nd and 3rd degree connections. Click on the profiles and see where the individuals work. This may identify companies of interest and will also show you information about the backgrounds of people who work there.

Tip 9: Blogs

Many thought leaders in each industry write sector specific blogs. Follow these individuals to keep up with the latest industry news, trends, and companies.

Tip 10: Web Searches

Search the internet for specific key words relevant to your area of interest to identify companies working in the area. Review the company websites and read pages such as, about us, company history, scientific advisors, advisory board, management team, investors, and partners. These pages provide useful information about the focus of the company and may help you learn about other companies. For example, the investors tab will often highlight the venture capital firm or firms that have invested in a particular company. Reviewing this page may help you identify a VC that you were unaware of. Review the VC’s webpage to learn about other companies that this firm invests in. Then add “companies of interest” to your “target company list”.

The amount of information available regarding companies, research, and exciting opportunities is staggering. By focusing your search efforts, you will uncover new and exciting companies aligned with your career aspirations. Tailor your approach to increase your effectiveness and efficiency, otherwise you may find yourself spending hours searching for that needle in the haystack. Through this process, you will learn about companies and the industry in which they work. The information you obtain will be invaluable as your career develops.

cookie monster

I am happy to report that Drosophila geneticists have not lost their sense of humor in the last 40 years. This paper from 2003 describes the cloning and characterization of a novel meiotic arrest gene, which they name cookie monster, “because the cells look like a whole bunch of cookie monster eyes”.

cookie monster and cookie monster- very similar don't you think?

Cookie monster is a meiotic arrest gene that plays an important role in spermatogenesis. In order to produce viable sperm, a large number of genes have to be transcribed in a specific sequence. This sequence is partially orchestrated by cookie monster, which binds to chromatin and facilitates the unwinding of this DNA-protein complex prior to engagement of RNA polymerase II.  In the absence of cookie monster, spermatocytes fail to complete meiosis, leading to sterile male flies Female flies don’t mind not having a cookie monster.

Reference:

J. Jiang, H. White-Cooper (2003) Transcriptional activation in Drosophila spermatogenesis involves the mutually dependent function of aly and a novel meiotic arrest gene cookie monster Development 130, 563-573.

Dancing Science

The seminal and most hilarious (in my opinion) science dance video on you tube, is the one where a rather large group of students danced the prokaryotic translation on a football field at Stanford in 1971.
Since the 70s quite a lot of science themed dance videos were posted on youtube, or wherever they got posted before youtube.  Sometimes they are part of biology classes in college and often hilariously bad.However dance and music are great ways to explain the basics of science to students who aren’t interested or have very little background. As for more complicated science: there is for example this great optical illusion, which really blurs the border between arts and science. And this video, which tries to explain the action potential by and to medical students via interpretive dance. Since the style is very similar to the original Stanford video, it can be assumed that they have at least been inspired be it.
There are also a couple of more professional science/music/advertising videos produced by large lab supply companies.
The “music videos of science” movement cumulates in the “Dance your PhD” contest which is held annually for the past 5 years and is sponsored by the AAAS. Last year’s competition included such diverse dances as the Generation of Haploid Stem Cells via Immaculate Conception with Ethanol to the tune of ‘I Get Knocked Down’ by Chumbawamba and Hydrogen Retention in Damaged Tungsten at High Surface Temperatures danced in a physics lab with great light effects. The winning video explained the formation of a superalloy using a mix of circus and silent movie. Entry into this year’s competition recently closed and the videos are now online. So if you have 30 minutes to spare have a look at them. I especially liked E.coli adapting to stress.

Oskar

I have previously written about Oscar, recently I found out that there is also Oskar which is is involved in Drosophila embryonic development. Oskar is transcribed from maternal mRNA and absolutely crucial for establishing the anterior-posterior axis of the developing embryo by localizing the germ line cells at the posterior pole of the embryo.

The red stain in this picture is Oskar mRNA at the posterior pole of the oocyte. The protein Oskar keeps other posterior determinates, such as Staufen in the correct location.

Unusually enough, Oskar is not an acronym, the authors (R.Lehman and C. Nuesslein-Vollhard), who described the gene decided to name it Oskar after the main character of the novel “the tin drum” by G.Grass : Oskar, a little boy refuses to grow up and stays a pre-teen throughout the novel spanning 30 years. This is similar to a drosophila embryo that is missing Oskar, it will never develop past the embryonic stage of its life. The authors explicitly state their naming in the materials and methods section.

and then even cite the novel in their references.

The novel was later adapted into a movie which won an Oscar. Here is a picture of Oskar from the movie, he doesn’t look like a protein or an embryonic fly at all.

How to identify “relevant” recruiters

by Lauren, CEO of propel careers

this post is reposted from the propel careers blog.

Finding a good recruiter who works in your area of interest can be extremely beneficial for your job search. With thousands of recruitment firms, ranging from one person companies that focus on specific roles, i.e. director level clinical affairs roles, to multinational organizations that focus on many functional areas and level of roles (c-level, VP, director, etc), how do you identify the one(s) which are relevant for you?

Search job boards

Recruiters often post roles on job boards to provide visibility and attract candidates to roles on which they are working. As you search these job boards (i.e. the MassBio Careers page, Indeed, Biospace), you may notice recruitment firms in addition to the biotech/pharmaceutical companies hiring directly. Make a list of these recruitment firms, research them, and email the relevant ones your resume. Some of these firms have newsletters and/or blogs that you can subscribe to which cover job openings, industry trends, and career development articles.

Ask connections

During your informational interviews, ask your connections if they know of recruiters who work in your area of interest. This will uncover recruitment firms that you can add to your list and may also provide you with a warm lead into a firm. Recruiters value referrals. Don’t be shy to email a recruiter and say, X person suggested that I reach out to you since you recruit for companies in the clinical research area.

Career Panels at Industry Conferences

Many industry conferences dedicate at least one panel during their conference to a career related topic. Pay attention to who is on the panel since these individuals may be recruiters relevant to your area.

LinkedIn

Search LinkedIn using the advanced search feature and then the keyword and title tabs. For keyword, type in “clinical research” and for title type in recruiter and then hit search. This will yield a number of recruiters (both internal and external to firms). You can then narrow this list by 1st, 2nd, 3rd degree connections, or geography via zipcode. When you identify recruiters of interest, add them to your list and email the recruiters, preferably via their email address. Most recruiters list their email address either in their LinkedIn profile or on their company website.

When you identify a recruitment firm, ask the firm what level of individuals they typically place. If you are a recent Ph.D. graduate and the firm only recruits at the C-level (CEO, CSO, CBO), they won’t be able to assist you. Also ask what type of roles the firm works on. If you want a research role and the firm only does financial roles in life sciences, again, they won’t be able to assist you. If they cannot help you, ask them if they know of other firms you should reach out to. Your diligence in this process will allow you to connect with “relevant” firms which should increase the chances for a successful outcome – a new job for you.

Popular Science Articles-Something for Everyone Part II

compiled by Noah

1. Why are there still so few women in science? (NYT Magazine, October 2013)

Women still unfortunately face many challenges in establishing a successful career in science. This article serves a timely reminder of these issues and also highlights a number of approaches which are being taken to increase the numbers of women in science and perhaps just as importantly to retain those who have had early career success.

2. End harassment (Nature, October 2013)

A powerful Nature editorial highlighting the sexual harassment often faced by women scientists and the measures that should be taken to crack down on this. Written in response to a recent scandal at Scientific American blogs which resulted in some brave, honest and open blog posts on the subject, see:

(a)  Jezebel

(b)  medium.com

(c) medium.com(2)

(d)  monicacatherine

3. A shot against Malaria (New Yorker, October 2013)

An overview of Phase III trial results of GlaxoSmithKline’s RTS,S/AS01 malaria vaccine candidate. This vaccine has been in development for almost thirty years and although it is much less efficacious than standard childhood vaccines, it may have the potential to moderately reduce the overall burden of disease caused by malaria in parts of Africa and South East Asia.

For an alternative viewpoint

4. What’s the point of finding cancer mutations (Slate, October 2013)

The author elegantly describes our increasing understanding of the genetic basis of cancer due in large part to the introduction of new sequencing technologies, but also highlights the lack of drugs which are currently available to exploit this new knowledge.

5. The last laughing death (The Global Mail, November 2012)

A brilliant account of Kuru, the devastating and fatal prion disease which was first reported in Papua New Guinea in 1957. Research into this disease has resulted in the recognition of a new form of infectious disease, a Nobel Prize and was invaluable in enabling rapid research into the cause of CJD in the UK in the 1990s.

RISE-intern

by Juliane

I like interns. I know that as a good postdoc (and PhD student for that matter) I should detest those time-sucking parasites, who need three hours to load an agarose gel, ask what temperature a 37C waterbath is at and manage to contaminate a cell line kept at 10x pen/strep. (the last paragraph is intended as sarcasm, however two out of three things really happened to me).

I like interns, because I like having new people in the lab, I like talking about my science and explaining it in layman’s term to an interested audience, I like how they make me think about my work, and I like teaching the next batch of potential scientists and hopefully make them like science as much as I do.

If you like interns as well or at least can live with them for a while you might consider taking a German RISE student next summer. RISE stands for research internships in science and engineering. German undergraduate students come to America or the UK to work in a lab for up to three months during their summer break. The DAAD (German academic exchange service) pays for their flights and accommodation. All you (or your PI) have to invest is some time and consumables.

With interns, as with all colleagues, you need luck. If you get lucky and get a brilliant intern, who is smart, interested, fun to work with and has good lab hands, you are set. He or she will help the project along, might even produce useful data and invite you all out for lab lunch.

Very few interns have all those abilities, just like very few technicians, PhD students, or fellow postdocs do, but when you get a RISE intern you have the choice between several applicants, so you can choose the one you think fits best to your working style.

Hosting a RISE intern is like a mini-trial run for the real deal (mentoring/supervising students in your own lab in the future): project design, choosing from several applications, supervising the work, making sure your intern learns something and has at least a little fun.

It lasts only three months, so why not give it a try.