PGFMA-Program 2008-2009 V5 - Instituto de Medicina Molecular

Transcrição

2008-2009
2
External Advisory Board
Erna Möller, Karolinska Institutet, Stockholm, Sweden
David Domingo Sabatini, NYU Medical Center, New York, USA
JMM van Dongen, Erasmus Medical Center, Rotterdam, The Netherlands
Selection Committee (2008-2009)
António Coutinho, IGC/FML
João Lobo Antunes, IMM/FML
Ricardo Brentani, Universidade de São Paulo
Isabel Palmeirim, Universidade do Minho
Miguel Castelo Branco, Universidade de Coimbra
Leonor Parreira, FML, Program Director
Course Organizers (2008-2009)
João António Augusto Ferreira MDPhD
Instituto de Medicina Molecular, FML, Lisboa
J. Melo-Cristino, MD, PhD
Tiago Fleming Outeiro, Ph.D
Domingos Henrique, PhD
Luís Graça, MD DPhil
Mónica Dias, PhD
Instituto Gulbenkian de Ciência, Oeiras
José Pereira Leal, PhD
Luis Moita, MDPhD
Gabriela Gomes, PhD
Raquel Seruca, MDPhD
IPATIMUP, Universidade do Porto
António Jacinto, PhD
Dan Holmberg, MDPhD
Ümea University, Sweden
Anna Tramontano
University La Sapienza, Rome
3
Gulbenkian Program 2008-2009
Students
Name
Specialty
Institution
Full-time
Ana Sofia Cerdeira
Gynecology & Obstetrics
Intern
H. Sto. António, Porto
Filipe Martins
Gynecology & Obstetrics
Intern
Hosp. Univ. Coimbra
Maria Rita Dionísio Abreu Oncology
Specialist
IPO Lisboa
Sandra Garcês Gama
Rheumatology
Intern
H. Garcia de Orta, Lisboa
Sofia Santos Braga
Oncology
Specialist
IPO Lisboa
Ana Bastos Carvalho
Ophthalmology
Intern
H. Sta. Maria, Lisboa
Joana Azevedo
Hematology
Intern
Centro Hosp. Coimbra
Nuno Leitão Figueiredo
General Surgery
Intern
Ricardo Fernandes
Pediatry
Intern
Teresa Lima Braga
General Surgery
Intern
Part-time
4
Gulbenkian Program 2008-2009. Faculty
BELGIUM
Ghent University Hospital, Ghent
BRASIL
Univ. Federal da Baía
Univ. Federal da Baía
CANADA
Univ. Simon Fraser
CROATIA
Univ. of Zagreb
FRANCE
Univ. of Montpellier II
Univ. de la Mediterranée, Marseille
HHMI, Necker Med School, Paris
Univ.de Nice-Sophia Antipolis
GERMANY
Children's Hospital, Heidelberg
Univ. of Cologne
Philipps-Universität, Marburg
Max Planck Institute, Martinsried
ITALY
Univ. Firenze, Ist. Toscano Tumori
Univ. La Sapienza, Rome
Milan, Italy
NETHERLANDS
Univ. Medical Center Groningen
Univ. Leiden
UK
Univ. Cambridge
Univ. Oxford
Guy's Hospital, London
Cancer Research UK, Cambridge
Univ. College, London (UCL)
Univ. College, London
Univ. College, London
Paterson Inst. Cancer Res, Manch.
Nat. Inst. Med Res, Mill Hill, Ld
London School of Hyg & Trop Med
Cambridge Cancer Center
EMBL Eur Bioinfo Inst, Cambridge
Imperial College, London
USA
Emory Univ. School Med, Atlanta
Harvard University
Harvard Medical School
Harvard University
Harvard University
NIH, Bethesda
Marc Mareel
Cancer
Sergio Cunha
Maurício Barreto
Epidemiology
Epidemiology
Fiona Brinkman
Computational Biology
Fran Borovecki
Neurodegenerative Disorders
Jamal Tazi
Jonathan Ewbank
J-L Casanova
Valérie Verhassel
Gene Expression
iRNA
Immune Disorders
Immune Disorders
Andreas E. Kulozik
Jonathan Howard
Martin Eilers
Erich Nigg
Gene Expression
Gene Expression
Cell Cycle & Disease
Lucio Luzzatto
Anna Tramontano
Adriana Miele
Giulio Cossu
Domenico Raimondo
Opening lecture
Structural Biology
Structural Biology
Regenerative Medicine
Structural Biology
Robert M.W Hofstra
Arn Maagdenberg
Cancer
Genetics
Miguel Constancia
Herman Waldmann
Michael Antoniou
James Brenton
Lewis Wolpert
J.T. Daniels
David Jones
Karamu Labib
Mike Blackman
Laura Rodrigues
Phil Jones
Dietrich Schumann
David Balding
Gene Expression
Immune Disorders
Gene Expression
Gene Expression
Structural Biology
Microbiology
Epidemiology
Epidemiology
Epidemiology
Keith Klugman
Judy Liberman
Marcia Haigis
Richard Colvin
Sean Eggan
Tim Mitchison
Crystal Mackall
Microbiology
iRNA
iRNA
Immune Disorders
John Edmunds
Corine Merle
5
J. Craig Venter Institute, Maryland
Univ. California San Francisco
Univ. of Philadelphia
SPAIN
Centro Nac. de Biotecnol, Madrid
Univ. Pompeu Fabra, Barcelona
SWEDEN
Univ. Ümea
Univ. Upssala
Univ. Upssala
SWITZERLAND
Ecole Polytechnique Federale de
Lausanne (EPFL)
Portugal
FC-UL
FCM-UNL/IPO-Lisboa
FML/IMM
FML/IMM
FML/IMM
FML/IMM
FML/IMM
FML/IMM
FML/IMM
FML/IMM
FML/HSM
FML
IBMC
IGC/IST
IG/FFUL
IGC
IGC
IGC
IGC
IGC
IGC
IGC, Fundação Champalimaud
INSA, Lisboa
IPO-Lisboa
ITQB
Instituto de Higiene Med. Tropical
Instituto de Higiene Med. Tropical
IPATIMUP
Laboratório Nac. Invest. Veterinária
Laboratório Nac. Med. Veterinária
Univ. Algarve
Univ. Coimbra
Univ. Porto, Faculdade de Medicina
Univ. Minho, Escol Ciências Saúde
Karen Nelson
M. Ramalho-Santos
Paul Muchowski
Arturo Alvarez-Buylla
Phong Tran
JM Valpuesta
N. Lopez-Bigas
Dan Holmberg
Martin Ingelsson
Richard Rosenqvist
Genetics
Genetics
Y-Barrandon
Jorge Pacheco
Manuel Abecassis
Leonor Saúde
Maria Mota
João Ferreira
José Melo Cristino
Luis Graça
Mário Ramirez
Pedro Simas
Margarida Carvalho
Thomas Hänscheid
Leonor Parreira
Helder Maiato
Álvaro Tavares
Carlos P. Gonçalves
Florence Janody
Gabriela Gomes
João Gonçalves
José Leal
Miguel Godinho
Mónica Bettencourt
Rui Costa
Luisa Romão
Paula Chaves
Cecília Arraiano
João Pinto
Pedro Cravo
Raquel Seruca
Miguel Fevereiro
Francisco Pinto
Leonor Cancela
Ana Cristina Rego
Armando T. Pinto
Isabel Palmeirim
Gene Expresion
Microbiology
Gene Expression
Microbiology
Immune Disorders
Microbiology
Microbiology
Gene Expression
Microbiology
Program Director
Genetics/Microbiology
Epidemiology
Microbiology
Aging
Gene Expresion
Gene Expression
Microbiology
Microbiology
Cancer
Microbiology
Microbiology
Gene Expression
Statistics
Gene Expression
6
Gulbenkian Program 2008-2009
Schedule
2008
October
S
5
M
6
T
7
November
W
T
F
S
1
2
3
4
8
9
S
M
T
W
T
December
F
S
S
1
5
6
T
W
T
F
S
1
2
3
4
5
6
8
9
10
11
2
3
7
8
7
10 11 12
13
12 13 14 15 16 17
18
9
10 11 12 13 14
15
14 15 16 17 18 19
20
19 20 21 22 23 24
25
16 17 18 19 20 21
22
21 22 23 24 25 26
27
23 24 25 26 27 28
29
28 29 30 31
26 27 28 29 30 31
4
M
30
Course
Organizer
OPENING LECTURE
Get together
GENE EXPRESSION
LAB VISITS/READING/DISCUSSIONS
STRUCTURAL BIOLOGY
CELL CYCLE & DISEASE
GENETICS
iRNA
COMPUTATIONAL BIOLOGY
STATISTICS & EPIDEMIOLOGY
FREE READING/DISCUSSIONS
Place
Lucio Luzzatto
Leonor Parreira
João Ferreira
Leonor Parreira
Anna Tramontano
Mónica Bettencourt
Dan Holmberg
Luis Moita
José Leal
Gabriela Gomes
Leonor Parreira
FCG
IMM & IGC
IMM
IMM or IGC
IGC
IGC
IGC
IMM
IGC
IGC
IGC
2009
January
S M
T W T
F
S
1
2
3
8
9
10
11 12 13 14 15
16
17
4
5
6
7
March
February
S
1
M
2
T
3
W
4
T
5
F
6
S
7
S
M T W T
F
1
2
6
7
8
9 10 11 12 13
14
3
4
5
S
8
9
10
11
12
13
14
15 16 17 18 19 20
21
16
17
18
19
20
21
22 23 24 25 26 27
28
23
24
25
26
27
28
29 30 31
18 19 20 21 22
23
24
15
25 26 27 28 29
30
31
22
Course
CANCER
IMMUNE DISORDERS
MICROBIOLOGY
AGING
DEV BIOL (Symposium)
NEURODEGENERATIVE DISORDERS
REGENERATIVE MEDICINE
ETHICS
PREPARING FOR RESEARCH
INTERVIEWS & EVALUATION
Organizer
Raquel Seruca
Luis Graça
Melo-Cristino
Rui Costa
António Jacinto
Tiago Outeiro
Domingos Henrique
João Lobo Antunes
António Jacinto
Selection Committee
Place
IPATIMUP
IMM
IMM
IGC
FCG
IMM
IMM
IMM
IMM
FCG
7
COURSES
Summary of contents
1 - GENE EXPRESSION
How genes command – an overview of eukaryotic gene control
6-18 October 2008
Organizer: João Ferreira, FML/IMM
AIMS
To provide a broad overview on how genes determine cellular and tissue activities.
Students should be able to understand with sufficient mechanistic detail how gene
activity impacts protein-based machineries to accomplish function. Also, how gene
expression programs operate via regulation at the transcriptional and posttranscriptional levels. Finally, the role of epigenetic modulation of gene expression
must be understood. Together, these concepts shall provide the basis for an informed
appraisal of the impact of modern biology in medicine (prevention, diagnosis and
therapy). This module shall also provide the background information on which
subsequent modules are predicated.
General topics
Transcriptional control of gene expression
Post-transcriptional gene control
Specific topics (examples of human disease)
1. Gene expression programs. How gene expression programs control
phenomena at the cellular and organismal level. Spatio-temporal regulation of gene
expression during development and differentiation - Hox genes as the paradigm. How
coordinatination between gene transcription, RNA processing and protein
synthesis/degradation is achieved in the context of a developmentally regulated gene
expression program – embryonic molecular clocks.
2. Splicing and splicing regulation. Splicing – the core reaction; regulation of
splicing and alternative splicing: relevance in normal and altered patterns of gene
expression.
3. Regulation of protein translation. Cytoplasmic control of protein translation
in health and disease.
4. Epigenetics. The impact of epigenetic regulation in gene expression.
Epigenetic reprogramming in stem cell plasticity and therapy.
By the end of the Gene Expression module the invited lecturers shall have provided a
broad overview of gene expression in humans and higher eukaryotes. Students shall
become aware of the complexities underlying regulation of gene expression and gene
networking to establish programs that influence cellular and tissue maintenance and
differentiation. In particular, it shall become clear how deregulation of gene expression
by genetic or/and epigenetic alteration impacts the emergence of the pathological
phenotype. It shall be understood that the smart design of drugs and therapeutic
vectors may require in some cases refined molecular detailing whereas in other cases
a broader, more comprehensive overview of the key alterations involved in disease
may prove more appropriate. Therefore, it shall become evident that a judicious
balance between reductionist and more holistic (systems biology oriented) approaches
may improve our current understanding of gene expression in health and disease, and
the planning of novel therapies.
8
Faculty
João Ferreira
Leonor Cancela
Cecília M. Arraiano
Isabel Palmeirim
Leonor Saúde
Margarida Carvalho
Carlos Farinha
Francisco Enguita
Miguel Constancia
Andreas E. Kulozik
Jamal Tazi
Michael Antoniou
Lewis Wolpert
Jonathan Howard
SCHEDULE:
Week 1:
a. Days 1-3:
b. Days 4-5:
Week 2
a. Days 1-2:
b. Days 3:
c. Days 4-5:
FML/IMM
CCMAR, Univ. do Algarve
ITQB
Univ. Minho
IMM/FML
FML
FCUL, Lisbon
IMM
Cambridge, UK
Children's Hospital, Heidelberg
Univ. of Montpellier II, France
Guy's Hospital, London
UCL, London
Cologne, Germany
General Topics
Specific topic – Gene expression programs
Specific topic – Splicing and splicing regulation
Specific topic – Regulation of protein translation
Specific topic - Epigenetic regulation of gene expression
1st Week (6-10 October)
Monday 6
9:30 – 10:30
11:00 – 12:00
13:00 – 14:00
15:00 – 17:30
Leonor Cancela
Francisco Enguita
IMM Seminar - Leonor Cancela
Students presentations/discussion of pre-selected scientific articles
LC and FE will dissect topic 1 (transcriptional regulation of gene expression) with
moderate detail. LC will provide a global perspective on how the modular functioning of
regulatory elements and the cellular “transcription factor environment” govern cell type
specific transcriptional programs. FE will lecture on how specific protein-protein and
DNA-protein interactions govern the assembly of the transcription machinery onto
regulatory elements to drive gene-specific transcriptional activation/repression. He will
also highlight (with low detail) the power of physical techniques to dissect key
molecular interactions occurring at the transcription unit. By the end of the first day
students shall understand how highly specific molecular interactions govern the activity
of specific sets of genes yet allowing flexibility and adaptation to intra- and extracellular cues.
9
Tuesday 7
9:30 – 10:30
11:00 – 12:00
15:00 – 17:30
Margarida Gama Carvalho
Luisa Romão
MGC and LR will dissect the mechanisms of splicing (MGC) and RNA quality control
(LR). MGC will also introduce the usefulness of broad-scale approaches to our current
understanding of coordination of gene expression at the post-transcriptional stage.
Students shall understand how these two major post-transcriptional mechanisms –
splicing and RNA quality control - coordinate to tailor the potential diversity of the
human genome in order to ensure proper cellular/organism function. Also, how
deregulation of these phenomena may lead to disease of blood (LR) and muscle
(MGC) cells.
Wednesday 8
9:30 – 10:30
11:00 – 12:00
15:00 – 17:30
Cecília Arraiano
Carlos M Farinha
CMF will highlight the impact of controlling protein production in the secretory pathway,
protein conformation and modification, and protein targeting to specific destinations
along the secretory pathway, highlighting the different levels of the cellular mechanisms
of quality control, to achieve a key goal of gene expression: "the right amount of the
right protein at the right time in the right place". The human genetic disease cystic
fibrosis will be used as a model to illustrate these processes. CA will focus on the
pervading role of microRNAs in gene expression from gene transcription to protein
translation. This will provide an important paradigm of how specific genes may
influence the activity of other genes at multiple steps of their expression. Also, the
relevance of bioinformatics and broad-scale analysis to disclosing real and predicted
functions of microRNAs will be stressed.
Thursday 9
10:00 – 12:00
Isabel Palmeirim
15:00 - 17:30
IP will lecture on how coordinated regulation of gene expression at different steps
(transcription, RNA and protein stability) generates molecular oscillatory mechanisms –
“molecular clocks” – to govern key events during embryogenesis.
Friday 10
10:00 – 12:00
15:00-16:00
Afternoon:
Leonor Saúde
IMM Seminar – João Lobo Antunes
Students meet with João Lobo Antunes
Preparation of student’s presentations for next monday (13th).
LS will provide an overview of how genes influence other genes (gene networking) to
set-up a transcriptional program in the context of embryonic development. LS will also
tell of the power of large-scale approaches to unravel novel networking partners.
JLA will deliver a seminar of broad, general interest entitled “Science and technology:
means or ends”.
17:00 Beer hour
10
2nd week (13-17 October)
Monday 13
10:00 – 11:30
Jamal Tazi
13:00 14:00
IMM Seminar - Jamal Tazi
JT will lecture on the targeting of the splicing reaction in the context of the HIV
infection. More specifically, how targeting the splicing of key HIV genes may be
achieved with major effects in the production of HIV particles but little effect on the
splicing of endogenous genes. Students shall understand how smart drug design and
testing may foster the development of drugs that display differential targeting of gene
expression (host vs pathogen).
Tuesday 14
10:00 – 11:30
Miguel Constância
13.00 -14.00
IMM Seminar –Maria João Saraiva
MC will lecture on the relevance of epigenetic effects in gene expression with a focus
on how epigenetic factors acting during development affect fetal programming of adult
disease and the metabolic syndrome (obesity, diabetes). MJS will deliver a seminar
entitled “Transthyretin deposition in an animal model of familial amyloidotic
polyneuropathy". The usefulness of animal models of human pathologies will be
highlighted.
All day:
Preparation of student´s presentations for next Wednesday (15th); the tutors for the
Gene Expression module shall be available.
Wednesday 15
9:30 – 10:30
Andreas Kulozik
11:00 – 12:00
Mike Antoniou
13:00 – 14:00
IMM Seminar - Andreas Kulozik
AK will lecture on the connections between trombophilia and 3´mRNA processing
efficiency. He will also address how the careful molecular analyses of specific types of
trombophilia in children helped to unravel novel important aspects of the 3´mRNA
processing mechanism.
MA will explain how smart design of therapeutic vectors is planned to achieve insertion
site independent, tissue type-specific expression of therapeutic genes. Students shall
understand how the basic knowledge regarding regulatory sequence elements and
tissue specificity of transcription factors, as well as regulation of chromatin structure, is
to be applied to this specific aim.
Thursday 16
All day: Preparation and presentation of papers selected by the students.
Friday 17
13.00 -14.00
Afternoon:
IMM Seminar - Jonathan Howard
Students meet Jonathan Howard
11
2 - STRUCTURAL BIOLOGY
27-31 October
Organizer: Anna Tramontano, University La Sapienza
The approximate program, assuming Monday morning to Friday lunch-time, is shown
below. I am expecting 1-1.5 hour lectures and 1.5-2 hours for each section of
practicals.
In case some of the students are facing a problem that involves a protein, I would like
to know which protein they are working on, so that we can use it as an example in the
practicals.
We will suggest a couple of books, articles for them to look at beforehand if they so
wish. They will then be given a copy of the presentations and at least one or two
papers authored by the lecturers at the time of the course.
Faculty
Ana Tramontano
Adriana Miele
Domenico Raimondo
David Jones
Univ La Sapienza, Rome, Italy
Univ College, London
Monday 27
Introduction to the course
Lecture - Protein structure determination I
Practical on structure determination
Lecture - Protein structure determination II
Tuesday 28
Lecture - Protein structure determination III
Lecture - Protein evolution
IGC Seminar
Practical on detecting evolutionary relationships
Wednesday 29
Lecture - Protein structure prediction by homology I
Practical on Protein structure prediction by
homology
Lecture - Examples of successful applications of
protein structure prediction by homology
Practical on Protein structure prediction by
homology
Thursday 30
Lecture - Protein structure prediction by fold
recognition
Practical on fold recognition
Lecture - Protein structure prediction by fragment
based methods
Practical on fragment based methods
Friday 31
Lecture - Other issues in protein structure
predictions: metaservers, disorder, etc
Practical on other methods
IGC Seminar
Anna Tramontano
Adriana Miele
Adriana Miele & D. Raimondo
Adriana Miele
Adriana Miele & D. raimondo
Adriana Miele
Adriana Miele & D. Raimondo
Anna Tramontano
IGC Seminar
Anna Tramontano & D Raimondo
Anna Tramontano
Anna Tramontano & D.
Raimondo
Anna Tramontano
Anna Tramontano & D.
Raimondo
David Jones
David Jones & D. Raimondo
David Jones
David Jones
IGC Seminar
12
3 - CELL CYCLE, CYTOSKELETON & DISEASE
3-7 November 08
Organizer: Mónica Bettencourt-Dias, IGC
Aims:
To learn the basis of cell cycle and tubulin cytoskeleton
To see good examples of basic research & the use of model organisms and how they
relate to human disease
To see examples of translational research in these fields
To be able to read basic biology papers and referee them
To be able to think of exciting questions in these fields and to propose research
projects to tackle them
To see the IGC and research done at IGC
Faculty
Phong Tran
Karim Labib
Helder Maiato
Erich Nigg
Florence Janody
Miguel Godinho
Monica Bettencourt Dias
Alvaro Tavares
Lars Jensen
Tim Mitchison
Martin Eilers
Monday 3
9.30-10.00
10.00 -11.30
12.00-12.30
12.30-13.00
14.30
16.30 –17.30
Tuesday 4
9.30-10.30
11.00-12.00
12.00-13.00
14.30-15.30
16-17.30
Wednesday 5
9.30-10.30
11.00-12.00
12.00-13.00
14.30-16.00
16.30-17.30
University of Philadelphia
Paterson Institute for Cancer Research
IBMC (Porto, Portugal)
Max Planck Institute, Martinsried
IGC
IGC
IGC
IGC
IGC
Philipps-Universität, Marburg
Organization of the course (papers the week before)
The Cytoskeleton & Human Disease
Phong Tran
(basics on actin and tubulin and a little bit of
research)
SNAPSHOT of my research on actin &
Florence Janody
cancer
guidelines- onwards- prepare Journal clubs
Prepare Journal clubs- 2 groups present, 2 groups criticize, 2 papers
related to cytoskeleton and 2 papers related to chromosomes
Basis of Cell Cycle
Alvaro Tavares
Journal club on cytoskeleton
DNA replication & Human Disease
IGC Seminar
Chromosomes & chromosome maintenance
Journal Club on chromosomes
Signalling and cancer
Seminar
Centrosomes & Cancer
Karim Labib
IGC Seminar
Karim´s seminar
Miguel Godinho
M.Bettencourt-Dias
& Paula Chaves
Prepare projects for next day- 3 projects- with help and discussion
from IGC students- projects on chromosomes, centrosomes &
cytoskeleton
13
Thursday 6
9.30-11.00
11.30-13.00
14.30-15.30
16-17.00
Friday 7
9.30-10.15
10.30-11.15
Project Presentation and discussion
Mitosis
about research in cell cycle and cancer
IGC Seminar
Helder Maiato
Tim Mitchison
Tim Mitchison
SNAPSHOT of my research on Epigenetics
Lars Jensen
and Centromeres
SNAPSHOT- Model organisms in drug
Rui Martinho
discovery
Big discussion with students on cell cycle & cancer
Centrosomes and cancer, research-talk
Erich Nigg
11.15- 12.00
12.00-13.00
Afternoon:
Divide in 2 groups: 3 hrs- discussion with students, their projects, etc
Live imaging at microscope (fly embryos), plus observing fixed cells under the
microscope
Scoring some flies
Passaging some cells; treating them with Taxol, fixing and staining for alpha tubulin,
actin and DNA
Yeasts
Beer and dinner
14
4 - GENETICS
10-14 November 2008
Organizer: Dan Holmberg, University of Umea
Aims - Not yet provided
Faculty
Dan Holmberg
Richard Rosenqvist
Arn van den Maagdenberg
Sofia Oliveira
Carlos Penha-Gonçalves
Univ. Ümea
Univ. Upssala
Univ. Leiden
IGC
IGC
Nov 10 Introduction to disease genetics, mapping
of monogenic and complex diseases
Cancer genetics
Nov 11 Animal models
IGC Seminar
Nov 12 Neurogenetics
"Journal club"
Nov 13 Genetics of cardiovascular disease
Genetics of infectious diseases
Overview of statistics in genetics
Nov 14 IGC Seminar
C. P- Goncalves
D Holmberg
Richard Rosenqvist
D Holmberg, C. P-Goncalves
IGC Seminar
Arn van den Maagdenberg
Sofia Oliveira
not yet named
not yet named
IGC Seminar
15
5 - RNAi: FROM MOLECULAR MECHANISM TO THERAPEUTICS
17-19 November 2008
Organizer: Luis Moita, IMM
Since RNA interference (RNAi) was discovered to work in mammalian cells, this
genetic manipulation technique has been hailed as a revolutionary new approach to
basic biological research and drug development and discovery. RNAi is expected to
provide critical insights into the mechanisms underlying human disease and
accelerating development of treatments for cancer, AIDS and a host of other disorders.
In addition, numerous proof-of-concept studies in animal models of human disease
demonstrate the broad potential application of RNAi therapeutics.
In this three-day course, we will discuss the biology of RNAi and its usefulness both in
discovery and therapeutics. We will transmit the experience of our team in gene
function discovery using RNAi and will complement it with that of several international
experts in basic and applied science working in this area.
Faculty
Luis F. Moita
João Gonçalves
Jonathan Ewbank
Richard Colvin
Judy Lieberman
Monday, 17th
9.30
10.00 -11.00
11.30 -12.30
14.30 -15.30
16.00 -16.30
16.30 -17.30
IMM
IMM
Centre d'Immunologie de Marseille-Luminy, Marseille
Harvard Medical School, Boston
Harvard Medical School, Boston
Welcome and course organization
Introduction and molecular mechanisms of
RNAi
Model Organisms, Part I: C. elegans
Model Organisms, Part II: D. melanogaster
and A. gambiae
RNAi in vertetebrates: Introduction
How to perform a screen: focus on an
arrayed screen
Luis F. Moita
Luis F. Moita
Jonathan Ewbank
Luis F. Moita
RicharColvin
th
Tuesday, 18
9.30 – 10.30
10.30 – 11.30
12.00 – 13.00
14.30 – 17.30
How to perform a screen: focus on a pooled
João Gonçalves
screen
RNAi based dissection of Immune responses Luis F. Moita
Seminar - RNAi screen reveals that
lysosomal exocytosis is required for
Richard Colvin
leukocyte chemotaxis
Students will divide in two groups. Each one will identify a biological
problem and will design a strategy to dissect and or correct it using
RNAi. In the following day, in the afternoon session, one group
presents while the other discusses the project proposed
Wednesday, 19th
9.30 – 11.30
Use of RNAi for therapy
12.00 – 13.00 IMM Seminar
14.30 – 16.30 presentations and discussion
17.00 – 17.30 Concluding remarks
Dinner
Judy Lieberman
Judy Lieberman
16
6 - COMPUTATIONAL BIOLOGY
20-25 November
Organizer: José Leal, IGC
High throughput technologies are revolutionizing biomedical research. Instead of
investigating single genes, proteins or metabolites we are now able to probe the entire
transcriptomes, proteomes, metabolomes, etc. This data deluge requires that we rely
more and more on computers and quantitative methods to interpret and derive
biological knowledge from this information. Such high throughput methods are
increasingly impacting our understanding of human disease, opening up new
diagnostic and therapeutic avenues. Above all, it asks from the clinician and researcher
alike to be able to interpret a whole new quality of information. In this one-week course
we will discuss the concepts underlying analysis of high throughput data, focusing on
their use in clinical research and in medical practice.
Faculty
José Leal
Lopez Bigas
Fiona Brinkman
Dietrich Rebholz Schumann
James Brent
David Balding
Karen Nelson
IGC
Univ. Pompeu Fabra
Univ Simon Fraser
EMBL European Bioinformatics Institute, Cambrigde
Cancer Research UK, Cambridge
Imperial College, London
The J. Craig Venter Institute, Maryland
17
7 - BIOSTATISTICS & EPIDEMIOLOGY
26 November-9 December
Organizer: Gabriela Gomes, IGC
I - Introduction to Biostatistics
26 November-3 December 2008
Instructor:
Classes:
Grading:
Armando Teixeira-Pinto ([email protected])
6 hours daily for 1 week (mixed theoretical and lab sessions)
Final exam (16 out of 20 points)
Assignments (4 out of 20 points)
Objectives:
In this course we will be studying basic methods of descriptive and inferential statistics
commonly used in health research. No previous knowledge of statistics is required.
There will be a strong emphasis on the application of these methods to real data
problems. Classes will be supported by the statistical software SPSS® and students
will be using individual computers during the course. After each session,
there will be a mandatory assignment due the day after.
At the end of the course, students should be able to recognize situations where the
statistical methods covered in the course can be applied; understand and verify their
assumptions; interpret the results; and be able to critique the statistical section and
results in medical literature.
Faculty:
Armando Pinto
FM-UP
Course topics:
1. Data (1h+1h)
2. Descriptive statistics (1:30h+1h)
3. Normal distribution and other
theoretical distributions. (1h)
4. Distribution of sample statistics and
confidence intervals (2h+1h)
Hypothesis testing (4h+3h)
6. Statistical power and sample size
calculation. (1h)
7. Diagnostic Tests (extra topic).
(2h+1h)
8. Correlation and simple linear
regression (2:30h+1h)
9. Basics of multiple linear regression:
(2h+1h)
types of data; data entry; data management.
frequency tables, summary measures
(location and dispersion); data presentation
(tables and graphs)
central limit theorem and the distribution of
the sample mean, standard error of the
mean, confidence intervals for the mean,
confidence intervals for proportions.
parametric tests (t test, One-Way ANOVA);
non-parametric tests - Mann-Whintey,
Kruskal-Wallis, Wilcoxon and qui-square
tests.
Bayes theorem, sensitivity, specificity,
likelihood ratio, false positives, false
positives, ROC curves
Pearson and Spearman correlatio
coefficients, the linear model assumptions,
interpretation of the regression parameters,
inference on the parameters estimates,
model checking.
interpretation of the regression parameters
model building
18
10.Introduction to logistic regression
(2h+1h)
11.Introduction to Survival Analysis
(extra topic):
the logit link, interpretation of the regression
parameters.
survival tables, Kaplan-Meyer
estimator, log rank test. (2h+1h)
Bibliography:
(required)
Pagano, Marcello; Gauvreau, Kimberlee. Princípios de bioestatística.
São Paulo: Pioneira Thomson Learning, 2004. 506p.
Swinscow,T D V. Statistics at Square One available at:
http://www.gulunap.unina.it/docu/Nutricam_statistics.pdf)
II - Introduction to Epidemiology
4-12 December 2008
Faculty
Armando Pinto
Gabriela Gomes
Laura Rodrigues
Sérgio Cunha
Corine Merle
John Edmunds
Maurício Barreto
FMUP
IGC
London School Hygiene &Tropical Medicine
ISC/UFBa
Univ. Baía
Objectives: Introduction to the main concepts, measurement and research strategies
used in epidemiology.
Thursday, 4 December:
Morning: What is Epidemiology? Definitions, History and Uses (Lecture/discussion) –
MB/LR
Afternoon: Infectious Diseases Epidemiology (Lecture/practice) – LR/MB
Friday, 5 December:
Morning: Measures of Frequency (Lecture/ practice) – MB/LR
IGC Seminar
Afternoon: Measures of Association (Lecture/ practice) – LR/MB
Saturday, 6 December:
Morning: Study Design: Overview and Randomized Controlled Trials (Lecture/practice)
– MB/LR
Afternoon: Study Design: Observational Studies – Prevalence, Case-Control, Cohort
(Lecture/practice) – LR/MB
Monday, 8 December:
Morning: Confounding (Lecture/practice) – SC/CM
Afternoon: Bias (Lecture/practice) – SC/CM
Tuesday, 9 December:
Morning: Validity (Lecture/practice) – SC/CM
IGC Seminar
Afternoon: Association and Causality (Lecture/practice) – SC/CM
19
Wednesday, 10 December:
Morning: Reading, interpretation and criticism of epidemiological papers – SC/CM
Afternoon: Reading, interpretation and criticism of epidemiological papers – SC/CM
Thursday, 11 December:
Morning: Mathematical Models in Infectious Diseases Epidemiology – GG
Afternoon: Models of Pathogen Evolution. Models of Contact Behaviour – GG/JE
Friday, 12 December:
Morning: Health Economics – JE
IGC Seminar
Afternoon: Problem solving – GG/JE
20
8 - CANCER
5 -16 January 2009
IPATIMUP (GABBA Program)
Organizer: Raquel Seruca, IPATIMUP
The aims:
The Oncobiology module will approach the biological/molecular mechanisms of cancer
development and progression. All sessions will be based on the discussion of clinical
cases followed by open discussions with the students about the underlying aetiological
factors (environmental and epigenetic) and the biological pathways underlying
pathological lesions.
The structure:
First week – lectures
Second week - morning lectures followed by lab-contact in the afternoon.
All sessions will have a common structure that should follow the following scheme.
1- Presentation of clinical case/s (sporadic or hereditary)
2- Pathological aspects of the tumours
3- Aetiology and molecular basis of the disease
4- Cellular effects mediated by the cancer associated factors
5- Signalling pathways involved
Faculty:
Senior Researchers and Professors at IPATIMUP. Post-Doc students.
Robert Hofstra, University Medical center Groningen, Holland
Marc Mareel, Ghent University Hospital, Ghent, Belgium
21
9 - IMMUNE DISORDERS
19-23 January 2009
Organizer: Luis Graça, FML/IMM
Aims:
To introduce cutting-edge immunology research and concepts. A few representative
topics related to current immunology were selected. These topics include: innate
immunity, cytokines, and immune regulation.
Proposed daily routine:
9.00 Introduction to the day (the basics for non-immunologists)
10.00 The broad context of the research topic (guest speaker or post-doc from group)
12.00 Research seminar
13.00 lunch break
14.30 Journal club and discussion (presentation of selected papers by students,
discussion with guests).
Faculty
Luis Graça
J-L Casanova
Crystal L. Mackall
Herman Waldmann
Valérie Verhassel
IMM/FML
Paris, France
NIH, Bethesda, USA
Oxford, UK
Nice, France
Topics
J-L Casanova, Paris. Pattern recognition receptors and immune deficiency, clinical
studies
Crystal L. Mackall, NIH, Bethesda. IL-7 influence on lymphocyte reconstitution, clinical
studies.
Herman Waldmann, Oxford. Immune regulation with monoclonal antibodies in
transplantation tolerance.
Luciano Adorini, BioXell, Milan. Immunomodulation of dendritic cells.
22
10. MICROBIOLOGY. Microbial challenges in today's and tomorrow's
medical practice
26-30 January, 2009
Organizer: J Melo Cristino, FML/IMM
Aims:
It is the aim of the module in Clinical Microbiology to discuss the state of the art in the
microbiologic diagnosis of infections; the ecology, epidemiology and population biology
of microbial pathogens; the current and future strategies for the prophylaxis of
infections and the molecular aspects of pathogenesis. To achieve these aims a
bacterium, a parasite and a virus were chosen as models.
The section dedicated to infections caused by Streptococcus pneumoniae will have a
strong focus on the recent paradigm shifts in the management of these infections. The
promises and pitfalls of novel diagnostic tools and the problem of antibiotic resistance
will be addressed. Emphasis will be provided on molecular epidemiology and the novel
understanding it is affording on the recent evolution and population biology of this
bacterium and their implications for our understanding of the infections it causes.
Dr. Keith Klugman (Division of Infectious Diseases, Emory University School of
Medicine, Atlanta, USA) will be our invited speaker. Dr. Klugman has a longstanding
interest in the pneumococcus and has been involved in the study of many aspects of its
ecology and evolution from a medical standpoint. Simple lab demonstrations are
planned to reinforce concepts discussed in the lectures.
The overall aim of the malaria´s days will be to give a general picture of the main areas
of research in the malaria field. We will focus on the areas studying basic biological
phenomena during the many Plasmodium life cycle stages. In particular, we will give
special emphasis to the pre-erythrocytic stages and to the more recent genomic
approaches.
Dr. Mike Blackman (National Institute for Medical Research, Mill Hill, London, UK) will
be our special invited speaker. His lab has been studying for many years the process
of parasite invasion of red blood cells, focusing on parasite proteases. Recently, his lab
has described in a CELL paper a new parasite secretory organelle that contains some
of these proteases that control parasite invasion. His experience studying basic biology
of a so important step of Plasmodium life cycle will be a beautiful example for the
students.
Influenza virus was chosen as the viral model system to illustrate basic concepts of
virus replication, pathogenesis, epidemiology and ecology. Particular relevance will be
put into why novel influenza viruses that circulate naturally in avian reservoirs emerge,
either through genetic reassortment or through direct transmission, in the human
population to cause pandemics. To this end, we intend to invite Dr Albert Ostrehaus
(Erasmus MC at the University of Rotterdam), who is particularly interested in viruses
that cross species barriers, are highly pathogenic and which cause disease globally.
His research is focused with working on a vaccine against avian flu, as well as studying
the pathogenesis and the host range, why the virus crosses the species barrier and
under what conditions. Dr. Osterhaus is also investigating the stability of the virus and
the possibility for genetic recombination and reassortment between different strains,
which could give rise to more dangerous infections. Dr. Osterhaus is an excellent
communicator thus inspiring for the students.
23
Faculty
José Melo Cristino
Mário Ramirez
Francisco Pinto
Maria Mota
Thomas Hänscheid
Pedro Simas
Miguel Fevereiro
João Pinto
Pedro Cravo
C. Penha-Gonçalves
Keith Klugman
Mike Blackman
FML/IMM
FML/IMM
IMM/FML
IMM/FML
FML
FML/IMM
LNIV
LNIV
IHMT
IGC
Emory University School of Medicine, Atlanta
Natl Institute for Medical Research, Mill Hill, London
24
11. AGING
2-4 February, 2009
Organizer: Rui Costa, IGC, Fundação Champalimaud
Not yet provided
25
12. NEURODEGENERATIVE DISORDERS
9-14 February, 2009
Organizer: Tiago Fleming Outeiro, IMM
Background
The complex three-dimensional structure adopted by a protein in the cell is vital for its
function. Oftentimes, as a consequence of environmental stress, genetic mutation,
and/or infection, the folded structure of a protein gets altered causing multiple proteins
to stick and fall out of solution in a process known as protein aggregation. These
aggregates are, in many instances, pathological hallmarks in many diseases known as
protein aggregation diseases. In protein aggregation diseases of the brain, incorrectly
folded proteins self-associate, form fiber-like aggregates and are associated with
neuronal cell death. In this course, the molecular and biochemical basis of protein
folding and misfolding, and its connection to neurodegenerative disorders such as the
prion diseases, Alzheimer's disease, Parkinson’s disease and Huntington's disease,
will be covered. The proteins involved in all of these disorders, how the proteins' three
dimensional structures change during the course of these afflictions, and the cellular
quality control systems used to cope with protein misfolding will also be covered
Finally, the course will address novel detection methods and therapies that are under
development to treat neurodegenerative disorders.
Faculty
José Maria Valpuesta
Martin Ingelsson,
Fran Borovecki,
Marcia Haigis,
Paul Muchowski,
Ana Cristina Rego,
Tiago Fleming Outeiro,
Joaquim Ferreira,
Centro Nacional de Biotecnologia, Madrid
Upssala
Univ. Zagreb
Univ. of California, San Francisco
Univ. de Coimbra
IMM
Hospital de Santa Maria
26
13. REGENERATIVE MEDICINE: FROM BIOLOGY TO THE CLINIC
16-21 February 2009
Organizer: Domingos Henrique,FML/IMM, Miguel Ramalho Santos Univ
California San Francisco
AIMS:
To present and discuss the most recent developments in the area of stem cell biology,
from the generation of embryonic stem cells to the isolation and characterization of
various adult stem cells. In addition, various approaches to stem cell-based therapies
will be discussed, with a critical evaluation of the field and future perspectives.
FACULTY
Domingos Henrique, FML/IMM
Miguel Ramalho-Santos, UCSF
Jorge Pacheco, FCUL
Manuel Abecassis, IPO
Freddy Radtke, EPFL, Lausanne, Switzerland
Phil Jones, Cambridge, UK
J.T. Daniels, UCL, UK
Giulio Cossu, Milan, Italy
Christine Mummery – Utrecht, Netherlands
Arturo Alvarez-Buylla, UCSF, USA
This Course will include Seminars by the invited speakers, followed by general
discussion of the topics. Students will have the opportunity to discuss selected papers
in Journal Club sessions.
27
14. Scientifc Integrity
25-27 February, 2009
Organizer: J Lobo Antunes, IMM/FML
Introduction to the topic - What it means, why it is important
Mentoring – What it means. Characteristics of the relationship. Selection of a mentor
Human experimentation – Ethical issues. Ethical codes. In formed consent. Special
populations. Special areas (embryo research). Ethical Committees
Clinical trials – Regulation. Financial implications. Conflicts of interest.
Animal experimentation. Ethical values. Codes of ethic regarding the use of animals.
Constraints.
Collaborative research – Nature of collaboration. Principles. Conflicts.
Scientific publications – authorship and peer review. The pressure to publish and not to
publish. Guidelines.
Ownership of data and intellectual property. Copyrights. Patents.
Genetic technology - Screening. Genetic manipulation. Control of information.
Scientific record – keeping
Faculty
Not yet provided
28
15. PREPARING FOR RESEARCH
2-13 March, 2009
Organizer: A. Jacinto, IMM
Not yet provided

PGFMA-Program 2008-2009 V5 - Instituto de Medicina Molecular

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