Download Example - UBC Pathology

R E SEAR C H P R O P O SA L
SUMMARY &
L AY S U M M A R Y
S EPTEMBER 1 1 , 2 0 1 2
GSS
M. Sadar+ H. Cote
1
EXAMPLES
CIHR SCHOLARSHIP
OPERATING GRANT
2
RESEARCH PROPOSAL SUMMARY
Description (structured summary)
• Title and summary that should be written with
the supervisor
• specific hypothesis of the research
• describe the candidate's role on the project
• written in general scientific language
• Maximum 1 page including references
• references can be written in a smaller font,
but must be legible
3
SUMMARY PAGE
BACKGROUND/INTRODUCTION
• Want to capture the attention and interest
of the reviewer
• Introduce the disease/health problem/field
• Provide a compelling rationale for why the
research needs to be done
– How many people affected?
– What is the cost to society/health care system?
– What is known/not known
4
SUMMARY PAGE
Background or Introduction
• End the section with a statement about WHY
and HOW you are undertaking the proposed
research, or a particular experiment
Examples:
"To identify molecular regulators of axonal guidance,
we will... " or
"To establish what family members think about genetic
testing, we will... "
5
SUMMARY PAGE
Hypothesis
• CIHR (as most other agencies) funds hypothesisbased research
• Provide a clear statement of your hypothesis
Examples:
“We hypothesize that [
] will [
].”
• Then follow with … "To test this hypothesis, we have
[three] Specific Aims (or objectives): ... ” [then state
these aims]
6
SUMMARY PAGE
Aims/Objectives
• Bulleted sentences or paragraphs that summarize
your specific aims (or objectives). WHAT you intend to
do
• Emphasize (bold) each aim/objective
Examples:
“Specific Aim 1 will determine…” or
”Objective 1: To determine...”
7
SUMMARY PAGE
Aims/Objectives
• Present clear and specific aims that will test
your hypothesis
• Aims must be feasible within your lab and
your proposed project timeline
• Aims have to be big enough to stand alone
(not just a few experiments)
8
SUMMARY PAGE
Methodology or Research Plan
• Brief summary of the methodology or HOW
you will do this
• Explain WHY you are using a specific strategy
if it is not obvious
• If needed, explain the statistical analysis plan
Example:
"Our approach will be to identify homologues of XXX
domain proteins expressed in the developing brain
using [xxx method]...”
“
9
SUMMARY PAGE
Significance
•
Concluding statement(s) that highlights the
significance and novelty of the work, including
immediate and tangible impact on health of
Canadians
•
Link back to disease if possible
• Want reviewer to think: YES!, this work should be done
Example:
"This work will enhance the understanding of the biology of... and to
provide a foundation for elucidating [disease].”
“ This research will identify new treatment targets for [disease] and
provide …toward new drug development”.
10
SUMMARY PAGE
General comments
• Write for scientist non-expert in your field of research
• Avoid jargon and define abbreviations
• Keep the topic focused, a story that makes sense
(don’t necessarily need to describe EVERYTHING
you plan to do)
• Write, then shorten
• Even though tight in space, keep “airy”
• Check spelling, grammar and punctuation
• Avoid references unless really necessary
11
SUMMARY PAGE
Main points to address
•
•
•
•
•
•
What is the problem?
Why it is important to do this research?
What you want to do?
How you will do it?
What the data will tell us?
For scholarship: what will your role be?
“I will contribute to the experimental design, be
responsible for […], will present results at […] and
write the manuscript derived from this work.”
12
EXAMPLE
Characterization of EPI-001 for the treatment of prostate cancer (Dr. Marianne Sadar, BC Cancer Agency)
Background: When prostate cancer progresses to the castration resistant stage, the average survival time is two years. Treatment options currently
available for patients with castration resistant prostate cancer (CRPC, also called hormone refractory or androgen independent) provide incremental
increases in survival (approximately 2 months). One mechanism suggested to play a role in CRPC is activation of the androgen receptor (AR) in the
absence of testicular androgens. Expression of many of the same genes that are increased by androgens become re-expressed in CRPC xenografts. This
suggests transactivation of the AR in spite of reduced levels of androgen which is consistent with nuclear localization of AR protein in secondary
prostate cancer tumors. Other data supporting the role of AR in CRCP include amplification of the AR gene, delayed onset of CRPC by altering the timing
and sequence of use of antiandrogens targeting the ligand-binding domain (LBD), the necessity of AR for the proliferation and tumor growth of
castration-recurrent prostate cancer cells, and the fact that the AR can be activated in the absence of androgen (and serum) by alternative signaling
pathways involving its N-terminal domain (NTD). The AR NTD contains the activation function-1 (AF-1) region that is necessary for transcriptional
activity to the AR, rather than AF-2 in the C-terminal ligand-binding domain (LBD), making the AR unique from other steroid receptors. Recent discovery
of constitutively active splice variants of the AR that lack the LBD emphasize that current therapies that target the LBD will not impact the growth of
CRPC that express these variants. Thus inhibitors to other domains of the AR are essential. The AR DBD shares high homology with other essential
steroid hormone receptors such as the glucocorticoid, mineralocorticoid, and progesterone receptors thereby making this a poor domain for drug
development. The AR NTD is intrinsically disordered and thought to require protein-protein interactions for induced folding to acquire transcriptional
activity. We identified EPI-001 as a first in class inhibitor to the AR NTD. The mechanism of action involves EPI-001 inhibition of essential protein-protein
interactions with the NTD that are required for transcriptional activity. Here we propose to examine known mechanisms of resistant for current
antiandrogens and androgen ablation therapies.
The hypotheses to be tested are that EPI-001 designed to target the AR NTD will inhibit the activity of gain-of-function mutations in the AR LBD induced
by antiandrogens, EPI-001 will show improved response in combination therapy, and resistance to EPI-001 will not occur by a mechanism of mutations
in the AR NTD. These hypotheses will be tested in 4 Specific Aims.
Specific Aims - Aim 1 will determine if resistance to EPI-001 will develop with long-term exposure. Aim 2 will examine if EPI-001 inhibits the activity of
clinically relevant AR mutations originally identified in patients with resistance to antiandrogens. Aim 3 will investigate if resistance to EPI-001 will
develop in vivo. Aim 4 will test EPI-001 in combination therapies with antiandrogens or docetaxel.
Significance - There are no long-term effective therapies for CRPC. We have identified the first inhibitor to the AR NTD which has attracted high
enthusiasm in the scientific and medical communities because of its potential as a therapy for lethal CRPC. The studies proposed here will yield insight
into the clinical application of EPI-001 and focuses on identifying its potential niche in the clinic (i.e., chemotherapy resistant, antiandrogen resistant
patient populations) and testing the possibility for resistance to develop.
13
EXAMPLE
Mitochondrial DNA damage in infants exposed to HIV antiretroviral drugs in-utero (Helene Cote)
Background: Exposure to antiretroviral nucleoside analogues in utero and neonatally has been associated with high serum lactate levels, and
mitochondrial DNA (mtDNA) depletion in infants born to HIV-infected (HIV+) mothers. This effect appears mostly reversible upon interruption of drug
exposure. Preliminary data collected as part of our ongoing studies of mitochondrial toxicity (mtDNA depletion) in infants born to HIV+ mothers suggest
that exposure to antiretroviral drugs, especially at conception or very early in embryonic development may be associated with significant mtDNA
damage (mtDNA mutations/deletions). The mitochondrial polymerase repair mechanism is relatively poor and mtDNA mutations, including those
nucleoside-induced, accumulate in the heteroplasmic genome over time. Congenital and acquired mtDNA mutations have been implicated in numerous
diseases and conditions, often associated with aging. Antiretroviral-induced mtDNA damage in the embryo may have unforeseen long-term effects for
the infants and their future offspring. We have an opportunity to evaluate mtDNA quality from two ongoing multicenter observational cohorts of infants
born to HIV+ mothers who were treated with antiretroviral drugs during their pregnancy.
Objectives: To determine whether exposure to antiretroviral drugs early in embryogenesis causes detectable mtDNA damage, which may have longterm unknown health consequences in the HIV uninfected antiretroviral-exposed population.
Hypothesis: Infants born to HIV+ mothers who received HAART during pregnancy will have significantly more mtDNA damage/mutations than infants
born to HIV-uninfected mothers and more so if drug exposure was at the time of conception as opposed to the 2nd or 3rd trimester of the pregnancy.
Research Plan: Study subjects will be infants born to HIV-infected mothers at three Ontario and B.C. hospitals and enrolled in two ongoing observational
mitochondrial toxicity studies. A blood sample is collected from the infant at the time of PKU testing, along with a blood sample from the mother.
Demographic data, treatment history, and other relevant information is also collected. DNA will be extracted from the blood and subjected to longtemplate PCR to amplify the whole mtDNA genome. The mtDNA consensus sequence will be compared between infants of two groups: exposed to
antiretrovirals in utero (N=70), and unexposed controls (N=42). Within the exposed group, exposure to HIV drugs at time of conception (N=20) will also
be compared to exposure only in 2nd or 3rd trimester of pregnancy (N=50). To compare the degree of heteroplasmy (mutations) present in the mtDNA
between these same groups, two regions (D-loop and ATPase 6) will be amplified by PCR and cloned from each infant and their mothers (N=50 for
exposed and 20 controls), and 96 sequences will be determined per subject. As mtDNA is maternally inherited, infant and mother mtDNA sequences will
also be analyzed for differences between them. Sampling size permitting, the effect of different antiretroviral drugs on mtDNA will also be investigated.
Significance: While the benefits of treating HIV+ pregnant women for the prevention of mother-to-child transmission of the HIV virus are undeniable,
the molecular effect of drug exposure during embryogenesis on mtDNA has not been studied in humans. Global treatment targets of “3 million by 2005
(3 by 5) will include treatment -with nucleoside-containing regimens- of young HIV+ women living in resource-poor settings, with limited reproductive
choices. It is imperative to understand as best we can the consequences on the mtDNA genome of conceiving while on HIV antiretroviral therapy. This
research will not only improve our understanding of the drug toxicity mechanisms, it may influence the timing and composition of antiretroviral therapy
received by HIV+ women of child-bearing age.
14
L AY SUMMARY
CIHR Scholarship language:
• Describe your project in a way that is accessible to a
lay audience
• Be sure to indicate how your proposed research can
improve personal health, the health of populations
and/or the health delivery system
• This information is used by CIHR to inform the public
and Parliament about the valuable research
supported through public funds
• Maximum of 2000 characters = this text x 6
15
L AY SUMMARY
• What makes your work interesting and
worth doing?
• How will your findings make a difference
in the health of Canadians?
• Typically the first thing the reviewer
reads → first impression
16
LAY ABSTRACT
Definition, purpose
• Not a ‘dumbed down’ version or research summary, nor a cut
and paste of it
• A clear, plain explanation of the research that anyone should
understand
• Must communicate to a wide audience
– Non-expert reviewers
– Patients/advocates
– Press releases
– Attracting donors
– Fund raising and government lobbying
17
LAY ABSTRACT
Definition, purpose
• Lay abstracts provide the context for the
research
• Purpose of the research, its background and
significance.
• Less important to explain methodology in
detail
• Describe the “big picture” and the gains
18
LAY ABSTRACT
The challenge
• Balance between over-simplification and
explaining the details of cutting-edge
research
• Balance between accuracy and
information overload
• Using lay language (your 15 year old niece
or grandmother should understand)
19
PROPRIETARY/CONFIDENTIAL INFORMATION
• No proprietary confidential
information!
GSS
M. Sadar
20
LAY ABSTRACT
Title
• Short and simple
• Grasps the main point
• Enticing
• Does not need to be the same as your
research proposal
21
LAY ABSTRACT
1st Sentence
• Crucial
• Need to engage the reader and invite
them to read on
• Try to explain your research in 25 words
and then use this as your first sentence
22
LAY ABSTRACT
How Lay is Lay Enough?
• Have a friend or a family member
point out the phrases and concepts
that they don’t understand.
• Ensure that the average person can
relate to the problem
23
EXAMPLE
24
EXAMPLE
Cellular aging in HIV-infected people
We all accumulate mutations within our mitochondrial DNA (mtDNA) which encodes proteins necessary
for our energy production. The more mutations we accumulate, the less we can produce energy, the less
we can maintain the health of our tissues. This mitochondrial aging is believed to be one of the main
reasons behind aging and age-related diseases. mtDNA mutations can be inherited or caused by
inflammation and oxidative stress. However, certain drugs such as the ones used to treat HIV are believed
to also induce mtDNA mutations.
Evidence is accumulating that HIV-infected people age faster than non-infected people. They have
diseases normally seen in older people earlier in life. It is unclear whether this is because of their HIV virus
(which can cause chronic inflammation) or because of the side effects of the antiretroviral drugs they take
to treat their disease. It is technically challenging to study mtDNA mutations because there are hundreds
of copies of mtDNA in each cell. We have developed a deep sequencing-based methodology to detect low
frequency mtDNA mutations and distinguish them from background PCR and sequencing errors. We will
use a cell culture model to determine whether commonly used HIV drugs can indeed induce mtDNA
mutations. We will also test samples collected from HIV+ and HIV- individuals, young and old, treated
with antiretroviral or not, as well as umbilical cord progenitor cells from infants born to HIV+ or HIVmothers, to investigate the relationship between mitochondrial aging, age, HIV infection and exposure to
HIV therapy. It is important to figure out what may accelerate aging in HIV+ individuals: the virus or the
medications?
25
GENERAL WRITING TIPS
• Shorter common words (e.g., use instead of utilize)
• Avoid complex logical arguments – be brief
• Short sentences (15-20 words)
• Write, then shorten
• Use analogies and relate science to everyday life
• Explain what key scientific terms mean
• Grade 10 level language
• Follow formatting guidelines
26