Advice on applying for an ERC Start Grant (part 1)

I was asked to give some advice on ERC Start Grant applicants, as a current grant holder. As this has come up several times I thought I would write a series of blog posts covering my hints and tips. Partly, this advice is specific to the ERC grant system, although most points are valid across any grant. In this first post I will deal the written application Part B1.

ERC Start Grant - Part B1

• Write every part of B1 in the context of the project that you are going to propose - fully utilise every section to sell your application
  
• In your CV you are selling yourself, not describing yourself. Identify your relative strengths and make them stand out. Perhaps you have lots of middle authorships in great journals – then put the journal impact factors in bold, so a quick scan of the page will highlight the great journals rather than your position on them. Perhaps you haven’t published in the top journals, but your work has gathered a disproportionate number of citations – then don’t put the journal impact factor in bold, instead put your individual number of citations in bold.
• Most importantly, when you are presenting your “scientific or scholarly contributions to the field” this is not a generic description. Use this to show how you are uniquely suited to run the project that you have proposed. For example, if you are proposing a project that melds skills you learned from your PhD and your post-doc, place special emphasis on these skills. Your career descriptions should be interwoven with the perspective of where you are going.
• Do not use the extended synopsis in Part B1 to simply summarise the project of Part B2. Use it to discuss the novelty of the approach or the concept. You do not know which part a reviewer will read first, so each document needs to be able to stand alone. Part B2 has a key function in showing that the outcome of your work will be important

Key tip: write about your career projection in the same way you write a scientific paper. You wouldn’t write “we investigated gene X, because of the twelve candidate genes the lab next door had a knockout of this one available”. Instead you would write up results that placed intent and direction in your activity, justifying gene X as your primary focus for a reason. Likewise, don’t describe your career trajectory as it actually occurred, “I did a PhD in metabolism, then my partner moved to Leuven so I looked for a post-doc and got offered one in dendritic cell biology”, rewrite it with intent and direction – “I have had a long-term interest on the impact of metabolism on the innate immune response, so in order to gain skills in both disciplines I first pursued a PhD in biochemistry and afterwards moved to a dendritic cell laboratory. Now I am able to utilise my training in both disciplines, with my independent laboratory focused on the effect of metabolic processes on monocyte activity.”

More hints and tips - Part B2 and the interview.

Scientific thought for the day

Richard Dawkins: "The power of a scientific theory may be measured as a ratio: the number of facts that it explains divided by the number of assumptions it needs to postulate in order to do the explaining."

Autoimmune Genetics Laboratory in the news

In De Staandard, 26th July

KUL en VIB boeken doorbraak in strijd tegen immuunziekten

De K.U.Leuven en het VIB (Vlaams Instituut voor Biotechnologie) hebben een stap voorwaarts gezet in de strijd tegen immuunziekten.

De onderzoekers ontdekten een nieuw type cellen dat kan helpen om het evenwicht te bewaren tussen een overactief en een onvoldoende actief immuunsysteem. Dat laten beide instellingen dinsdag weten in een mededeling.

Talloze mensen lijden aan een ziekte van het afweer- of het immuunsysteem. Als het systeem overactief is, kan dat leiden tot allergieën en auto-immuunziekten zoals Systemische lupus erythematosus (afgekort SLE), een aandoening waarbij het afweersysteem zich op overdreven wijze tegen het eigen lichaam richt. Maar is het afweersysteem onvoldoende actief, dan treden infecties of tumoren op. Het juiste evenwicht vinden, is dus essentieel.

Adrian Liston, van het VIB en de K.U.Leuven, is een nieuw type cellen op het spoor die helpen om dat evenwicht te bewaren. De ’folliculaire regulatorische T-cellen’ (Tfrs) zetten een rem op de groei van afweercellen die antistoffen aanmaken. Verder onderzoek zal het uiteindelijke belang van de Tfr-cellen moeten uitwijzen.

In Het Nieuwsblad, 26th July

KUL en VIB boeken doorbraak in strijd tegen immuunziekten

De K.U.Leuven en het VIB (Vlaams Instituut voor Biotechnologie) hebben een stap voorwaarts gezet in de strijd tegen immuunziekten.

De onderzoekers ontdekten een nieuw type cellen dat kan helpen om het evenwicht te bewaren tussen een overactief en een onvoldoende actief immuunsysteem. Dat laten beide instellingen dinsdag weten in een mededeling.

Talloze mensen lijden aan een ziekte van het afweer- of het immuunsysteem. Als het systeem overactief is, kan dat leiden tot allergieën en auto-immuunziekten zoals Systemische lupus erythematosus (afgekort SLE), een aandoening waarbij het afweersysteem zich op overdreven wijze tegen het eigen lichaam richt. Maar is het afweersysteem onvoldoende actief, dan treden infecties of tumoren op. Het juiste evenwicht vinden, is dus essentieel.

Adrian Liston, van het VIB en de K.U.Leuven, is een nieuw type cellen op het spoor die helpen om dat evenwicht te bewaren. De ’folliculaire regulatorische T-cellen’ (Tfrs) zetten een rem op de groei van afweercellen die antistoffen aanmaken. Verder onderzoek zal het uiteindelijke belang van de Tfr-cellen moeten uitwijzen.

Balance of the immune system determined by newly discovered T cells

From the VIB Press release: A newly discovered cell type helps to determine the balance of the immune system. The cells are derived from FoxP3(+) regulatory T cells, which recently have been demonstrated to suppress disease during transplantation. Nature Medicine and Blood, two high-ranking scientific journals, are publishing findings by the Autoimmune Genetics Laboratory about this discovery.

 

Innumerable people suffer from immune system disorders. If the immune system is overactive, it can result in allergies and autoimmune diseases such as Systemic lupus erythematosus (SLE). If the immune system is not active enough, infections or tumors occur. It is therefore essential to maintain the right balance.

 

The Autoimmune Genetics Laboratory is investigating a new type of cell that helps to maintain this balance. These ‘follicular regulatory T cells’ (Tfrs) suppress the process by which antibodies are produced during infections and SLE. The Tfrs themselves are daughter cells of FoxP3(+) T cells, key regulators of the immune system.

 

From lupus to cancer

In order to prevent disease the immune system needs to be in balance. If the system is too active, it produces antibodies against harmless substances, as is the case with allergies. An overactive immune system can even attack the body’s own tissues, causing autoimmune diseases such as lupus, rheumatism and diabetes. However, an insufficiently active immune system opens the way for rampant infections and tumors.

 

A complex network of regulatory cells is active to maintain this balance in our bodies. This must ensure that the immune system is sufficiently active and selective so that pathogenic intruders are recognized and eliminated in good time, but at the same time that it does not get out of control. This network of regulatory and activating cells is a long way from being fully unraveled. Dozens of researchers around the world are working to map this network.

 

This Tfr research is a joint collaboration between researchers from VIB-K.U.Leuven, the Australian National University (Aus) and the University of Cambridge (U.K.).

 

Publications

Linterman et al, Foxp3(+) follicular regulatory T cells control the germinal center response, Nat Med, 2011, doi:10.1038/nm.2425

 

Tian et al, Foxp3+ regulatory T cells exert asymmetric control over murine helper responses by inducing Th2 cell apoptosis, Blood, 2011, doi:10.1182/blood-2011-04-346056

FWO post-doctoral fellowship awarded to Bénédicte Cauwe

This week it was announced that Dr Bénédicte Cauwe won an FWO post-doctoral fellowship to perform research in the Autoimmune Genetics Laboratory. Dr Cauwe recently finished her PhD in the laboratory of Professor Ghislain Opdenakker at the Rega Institute and will continue her research on systemic lupus erythematosus at the Autoimmune Genetics Laboratory.

Academic independence

What is academic independence?

In the mind of many a post-doc it is quite simple, it is the freedom that you gain when you step up from being a post-doc to becoming a faculty member. As a post-doc, your principle investigator has the final say over your research program, while as a faculty member you are the principle investigator.

It seems straight-forward, but in practice the distinction can be quite blurred. As a senior PhD student in the Goodnow laboratory I effectively had academic independence. My principle investigator had funding and placed trust in me so that I could run my research more or less independently. Hopefully the PhD students in our laboratory feel the same way. Could I have done any hair-brained project I wanted to? Certainly not, it had to be within reason, but the research interests I had were aligned with that of my mentor, so in effect I had the independence to pursue the research that I wanted to pursue.

This is not qualitatively different from the academic independence I have now as a faculty member. Yes, I can chose the research program that I want to pursue, but again the within reason proviso applies. I no longer have a faculty member above me, acting as the final arbiter, but there are still limitations. The most obvious limitation is the grant review process. If I want to do an experiment I require funding, which necessitates my research aims being in line with the granting body and being approved by a panel of experts. Then of course, as junior faculty, I will have a jury over-looking my renewal. These juries invariably have something to say about the direction of your science - your research interests are too broad/too narrow, you are spending too much/ too little time on collaborative ventures, etc. In the modern "big science" era, your colleagues and collaborators form another restraint - you may need to negotiate for time on certain equipment or access to particular samples.

Some of these restraints may be reduced over time, but unless you are a Nobel Prize winner with guaranteed block funding for life there will always be some limitations to academic independence. Perhaps the biggest difference in the academic freedom between a post-doc and faculty member is the diffusion and immediacy of responsibility. As a post-doctoral fellow, the limitations on your research are concentrated in a single person who can have immediate impact - a particular line of research can be shut down today with a single decision. As a faculty member, by contrast, the limitations on your research are delayed and the decision-making capacity is diluted out into a plethora of juries. If one grant foundation chooses not to support your work, another (with a distinct jury) may, and often there are avenues for pursuing research for some months or even years without direct funding.

So rather than the qualitative leap in academic independence that a faculty position represents to some, perhaps it is more accurate to think of a gradual shift in responsibility. Someone moving from a post-doctoral position in a restrictive laboratory to a well-funded start-up faculty position will feel an enormous leap in academic freedom. But for others, being a senior post-doc in a rich laboratory supervised by a figure of benign neglect, the entry into a world of constant grant review may even result in a loss of freedom to pursue your research interest.

IRO fellowship won by Dina Danso-Abeam

Today it was announced that Ms Dina Danso-Abeam in the Autoimmune Genetics Laboratory was awarded an IRO fellowship to perform research towards her PhD. 

An alternative model for peer review

There is no doubt that the current model of peer review is an effective but inefficient system. The high quality of publications that complete peer review is a testomy to the effectivity of the peer review system, as poor papers rarely get accepted in well reviewed journals. However the efficiency of the review system is very low.

Consider that the highest ranked journals have acceptance rates of around 10% and even the middle-ranked journals have acceptance rates of less than 50%. Most papers get published sooner or later, but with the career reward of publishing in high impact factor journals, it is not unusual for a publication to get rejected four or five times as the authors work their way down the journal ranking list. Considering that each review will generally consist of three reviewers, a single paper that had a tough time could consume the (unpaid) time of fifteen reviewers before it is finally accepted. This is an enormous burden on the scientific community, and is largely a wasted burden - afterall, each journal editor only gets to see three of those fifteen reviews when making a decision to accept or decline an article. It also considerably slows down the dissemination of information, as it is not unusual for the entire review process to consume a year or more.

So let's consider an alternative model for peer review, one which keeps the critical aspects that provide effectiveness, but which changes the policies that produce inefficiency. Consider now a consortium of four or five publishers, which may include 20 journals that publish papers on immunology. Rather than authors submit to the individual journals, the authors would submit to a centralised editorial staff, which is paid for by the publishers but which is independent of each journal. An immediate advantage would be the ability to have many more specialised editors available, allowing for better decisions on choosing and assessing the reviews.

Each paper would then be sent out to five or six reviewers, and the reviews would be made available to each of the journals. The editorial staff at the journals would be able to make an assessment of the paper and put forward an option to accept, conditionally accept or decline the paper. This information would be transmitted back to the consortium, and would be provided to the authors. The authors would then be able to make their choice of which offer to accept. In effect, each journal would be making a blind offer to the authors to publish their paper, with full knowledge of the reviews but without the knowledge of whether the other journals put in a bid.

Consider the benefits of this alternative model to each player:

1. The journal gets to judge on more complete information, with double the number of reviews available for each paper, selected by more specialised editorial staff.

2. The reviewing community will more than halve the number of reviews required, while actually providing more information to the journals.

3. The authors will no longer have to make strategic decisions in choosing where to submit, they will simply submit to the consortium and have the option to publish in the top ranked journal which is interested in the paper.

4. The scientific community will have access to cutting-edge research months or even years earlier than under the current system.

The verdict on Andrew Wakefield: Fraud

In 1998 Andrew Wakefield published a paper which has severely damaged public health in the last ten years. Based on his observations of only twelve children, nine that he claimed had autism, and without a control group, he concluded that the measles/mumps/rubella vaccine caused autism. As a hypothesis, this was fine, unlikely, but not impossible. He saw nine children with autism, reported that their parents linked this onset with the MMR vaccine, and put it in the literature. Why on earth on underpowered observation like this made it into the Lancet is beyond me, but there is nothing wrong with even outlandish hypotheses being published in the scientific literature. Was it a real observation, or just an effect of a small sample size? Was it a causative link, or just due to coincidence in timing?

As with any controversial hypothesis, after this one was published a large number of good scientists went out and tested it. It was tested over and over and over again, and the results are conclusive - there is no link between the MMR vaccine and autism.

In itself, this was of no shame to Andrew Wakefield. Every creative scientist comes up with multiple hypotheses that end up being wrong. People publish hypotheses all the time, then disprove them themselves or have them disproven by others. If you can't admit being wrong, you can't do science, and it is in fact the mark of a good scientist to be able to generate hypotheses that others seek to knock down. Ten of the thirteen authors on the study were able to see the new data and renounce the hypothesis.

The shame to Andrew Wakefield is not that his hypothesis was wrong. No, the shame he has brought upon himself was by being unscientific, unscrupulous and unethical:

1. Firstly, Wakefield did not present his paper as a hypothesis generator, to be tested by independent scientists. Instead he went straight to the media and made the outrageous claim that his paper was evidence that the MMR vaccine should be stopped. This is not the way science or medicine works and was a conclusion unsupported by the data. Worst of all it was a conclusion that many parents without scientific training were tricked into believing. Vaccination rates for MMR went down (autism rates have remained unchanged) and children started dying again of easily preventable childhood diseases. A doctor does not see half a dozen children that developed leukemia after joining a football team and then hold a press conference telling parents that playing sports causes cancer in children, which is the direct equivalent of Wakefield's actions.
2. Secondly, it has now been conclusively demonstrated that his original data was fraudulent. Interviews with the parents of the original nine children with autism show that he faked much of the data of the time of onset, taking cases where autism started before the MMR vaccine and reversing the dates to suggest that the vaccine started the autism. Analysis of the medical records of these children show that as well as the timing being incorrect, many of the symptoms were simply faked and non-existent. The evidence on this charge alone makes Wakefield guilty of professional misconduct and criminal fraud.
3. Thirdly, unknown to the coauthors of the study and the parents of the children, Wakefield had a financial conflict of interest. Before the study had begun, Wakefield had been paid £435 643 to find a link between vaccines and disease as part of a lawsuit. Every scientist must disclose their financial interests in publication so that possible conflicts are known - Wakefield did not. If he had disclosed this to the press conferences the media may have been slightly more skeptical about his outlandish claims.

These last two issues, scientific misconduct and financial conflict of interest, are the reason why the paper was formally retracted by the Lancet. Studies that are wrong don't get retracted, they just get swamped by correct data and gradually forgotten. Instead, the retraction indicates that the Wakefield paper was fradulent and should never have been published in the first place. Likewise, the British General Medical Council investigated the matter and found that Wakefield "failed in his duties as a responsible consultant" and acted "dishonestly and irresponsibly", and thus struck him off the medical registry.

The worst part about this sorry affair is that it is still dampening down vaccination rates. Literally hundreds of studies, with a combined cohort size of a million children, have found no link between the MMR vaccine and autism, yet one fraudulent and retracted study of nine children is still talked about by parents. Some parents are withholding this lifesaving medical treatment from their children, and their good intentions do nothing to mitigate the fact that cases of measles and mumps are now more than 10 times more likely than they were in 1998, and confirmed deaths have resulted. And Andrew Wakefield, the discredited and disbarred doctor who started this all? Making big money in the US by selling fear to worried parents, and deadly disease to children who have no say in it at all.



The Autoimmune Genetics Laboratory in 2010

All the members of the Autoimmune Genetics Laboratory, at our end of year dinner.