The PAPSummer program was initiated in 2015 with the goal of providing the opportunity for Portuguese college students or recent college graduates to do one-month internships at companies, universities, or research centers, in the USA or Canada, preferably under the supervision of a PAPS member. More information here.

The first edition of this program, PAPSummer 2015, received more than 500 applications from Portuguese students from different geographic locations and backgrounds. Eight Portuguese students were awarded a PAPSummer fellowship in 2015 and developed internship projects at renowned universities and companies such as the Harvard Medical School, the Space Telescope Science Institute (NASA), the Portuguese Consulate of New York, and the consulting company Axis Advisors.

Title: “Experimental evolution of genetic instability during a yeast model of cancer progression”
Field: Biology, biochemistry, evolution
City: Boston, MA
Supervisor: Miguel Costa Coelho
Affiliation: FAS Center for Systems Biology, Harvard University

Life depends on the faithful transmission of genetic information. During cancer progression, the selection for successive mutations favors the evolution of genetic instability (GI), characterized by increased mutation rates. However, it is not clear how GI ­ defects in DNA repair/replication, chromosome rearrangements or loss ­ arises and evolves. By placing yeast cells under selective pressure to inactivate growth suppression, similarly to what occurs in tumors, we have evolved and quantified GI in three genetic architectures: 1) haploids, 2) diploids heterozygous for the growth suppressor gene, and 3) most similar to cancer – diploids homozygous for the growth suppressor gene.

One mutation is sufficient to cause GI in the evolved clones, but in some clones >1 mutations contribute to GI. Using mutation segregation analysis and whole genome sequencing we identified both loss­of­function and putative gain­ of­function mutations, also in essential genes, that drive GI. There were 3 prevalent classes of mutations: 1) DNA repair, 2) Protein stability and 3) Mitochondrial genes. To test whether these mutations were causative, we re­ engineered them back into the ancestor, time traveling to test the origin of instability. For a subset of genes in each class, the re­engineered mutation increased GI, proving causality. Conversely, replacing the mutated allele with the wild­type copy in the evolved clone restored genetic stability. The majority of the mutations we discovered lie in genes not previously related to GI in yeast, and half are related to human cancer genes.

In contrast to classic screens where gene deletions were used, to unbiasedly select for increased mutation rate allows evolution to tell us how GI arises. We will proceed to functionally test how protein stability or mitochondrial disfunction affect GI, and analyze the mutational signatures of the evolved GI, focusing on conserved genes to bridge our work with human cancer.

Title: “Cloud-based NGS Data Processing”
Field: Computational Genomics
City: Long Island, NY
Supervisor: Jonas Almeida
Affiliation: Stony Brook University

O desenvolvimento de NGS (next generation sequencing), transformou a sequenciação genómica num método laboratorial rotineiro. Desta forma o desafio passa do processamento da amostra para o processamento da grande abundancia de dados que são assim gerados. Este estágio está inserido num projecto de genómica da evolução da resistência a antibióticos em Streptococcus pneumoniae, e tem como objectivo familiarizar o participante com a execução de métodos computacionais de NGS na nuvem (por exemplo usando dnaNexus) e na representação dos resultados da análise na forma de uma aplicação em rede.

Title: “When Myonuclear Positioning Goes Wrong”
Field: Developmental biology
City: New York, NY
Supervisor: Mafalda Azevedo
Affiliation: Memorial Sloan-Kettering Cancer Center

Mammalian skeletal muscle is composed of bundles of multinucleated myofibers. Myonuclei reside above the sarcomere at the periphery of the muscle fiber and are positioned to maximize their internuclear distance. Mispositioned myonuclei are a hallmark of many muscle disorders, such as Centronuclear Myopathies and Emery-Dreifuss Muscular Dystrophy, and have been used diagnostically for decades.

Nevertheless, the mechanisms driving myonuclear positioning remain unclear.

To understand the mechanisms involved in myonuclear positioning, you will use Drosophila melanogaster (fruit fly) as a model organism. Drosophila serves as a simple and rapid system to investigate the basic mechanisms of myonuclear positioning and its effects on muscle function/physiology. Data from our lab indicate that there is a striking correlation between aberrantly placed and clumped nuclei and a decrease in muscle function. Given the strong conservation of genes and mechanisms between the fruit fly and mammals, aberrant myonuclear positioning could contribute to the muscle deficits associated with muscle disease. Taking advantage of this model organism we will be assessing myonuclear positioning in two different stages of the Drosophila development: the embryonic and the larval stages.

Title: “Empirical Verification of the S I, Fe I, and Ni II Oscillator Strengths in the HST/STIS bandpass”
Field: Astronomy, astrophysics
City: Baltimore, MD
Supervisor: Cristina Oliveira
Affiliation: Space Telescope Science Institute

The measurement and analysis of metal absorption lines in the spectra of distant stars and galaxies provides the basis for much of our understanding of the content, physical conditions, and evolution of the interstellar medium of galaxies, the circumgalactic medium of high redshift systems, chemical feedback in galaxies, how black holes accrete matter and grow through cosmic time, how did the universe become ionized, to name just a few topics. Critical to such absorption line spectroscopic measurements are the oscillator strengths, f-values, of the different atomic transitions for each element. The project of the PAPS Summer student will be to use the data and measurements already performed for S I, Fe I, and Ni II to determine updated oscillator strengths for some transitions which were found to have incorrect oscillator strengths during work performed recently. The student will start by evaluating all absorption line measurements already performed using the spectra of four stars to determine exactly which transitions might have incorrect f-values. The student will then do a literature seach to determine if any new theoretical or laboratory measurements are available for the questionable f-values. He/She will then use robust f-values to anchor the absorption line measurements and determine updated f-values, including uncertainties.

Title: “Genetic Modifiers of CAG Repeat Instability in Huntington’s Disease”
Field: Neurogenetics, molecular biology
City: Boston, MA
Supervisor: Ricardo Mouro Pinto
Affiliation: Massachusetts General Hospital, Harvard Medical School

The project will initially involve molecular biology and cloning techniques to generate constructs co-expressing Cas9 and sgRNAs for the 4 MMR genes (Msh2, Msh3, Mlh1 and Mlh3) which have been previously confirmed as enhancers of somatic CAG instability in our HD knockin mice. The ability to efficiently edit these target genes will be subsequently investigated by transfection into mouse fibroblast cell lines followed by T7 endonuclease 1 assays. Knockout efficacy will also be assessed by target gene expression analysis by qRT-PCR and Western Blotting. If time allows, these experiments will be extended to novel candidate genetic modifiers.

Title: “Communication and Public Diplomacy”
Field: Graphic and editorial design, information technology
City: New York, NY
Supervisor: Manuela Bairos
Affiliation: General Consulate of Portugal in New York

O Consulado-Geral em NY foi recentemente reativado e pretende desenvolver uma estratégia de diplomacia pública visando modernizar e dinamizar a inter- ação com os seus utentes e com o público em geral. O estágio deverá incidir sobre a identificação e desenvolvimento do potencial de instrumentos disponíveis para atingir esse público alvo (website, redes sociais, newsbriefs, revista, etc) e na realização de um levantamento e contactos com parceiros em NY e em Portugal nas áreas de atuação do Consulado que possam apoiar a promoção de Portugal.

Title: “Financial Planning, Wealth and Risk Management Planning”
Field: Investment management, financial planning
City: Providence, RI
Supervisor: Daniel da Ponte
Affiliation: Axis Advisors, LLC and Rhode Island Senate

Axis Advisors, LLC is a registered investment advisor with offices in East Providence, RI and Westport, MA. As a fee-only independent wealth management and financial planning firm, we work alongside our clients and are fiduciaries for their best interests. We work with individuals and families, businesses and non-profit organizations to develop and manage their financial, investment and retirement plans. We do not have or sell any proprietary products and our fee structure is transparent to our clients. We’ve built a reputation for taking an approach to investing and managing assets that is aligned with our clients goals and objectives. We believe that by helping our clients identify their goals and by providing them with objective advice, we can help make financial decisions based on a well thought out strategy. Our holistic approach to wealth management, financial and insurance planning takes into account all of the aspects of a client’s life and how they are connected. We create a plan that is specific to them. The intern we receive from PAPSummer will be exposed to the business side of managing a firm on a day to day basis. Once they are provided an overview of the firm and resources, they will be asked to perform research and participate in client meetings. Specific areas of exposure will be investment management research, financial planning software modules and an opportunities to develop hypothetical investment programs and financial plans. Intern may be asked to perform minor clerical work that is directly related to managing client relationship and client management systems. Intern must sign a confidentiality agreement upon commencement of their internship.

The second edition of this program, PAPSummer 2016, was again very successful. It received applications from close to 250 Portuguese students from different geographic locations and backgrounds. Five Portuguese students were awarded a PAPSummer fellowship in 2016 and developed internship projects in areas from cinema to biology/medicine to astrophysics, in renowned US institutions.

Title: “Short movie: Vozes na Névoa”
Field: Cinema
City: New York, NY and Bedford, MA
Supervisor: Pedro Marnoto Pereira
Affiliation: Park Bench Pictures

O projeto “Vozes da Névoa” pretende fazer uma exploração da pesca do bacalhau nos bancos da Terra Nova pelos portugueses, assim como a sua relação com a emigração lusitana para os EUA em meados do século XX. Para isso, realizer-se-ão entrevistas com antigos bacalhoeiros portugueses residentes em New Bedford, com o objectivo de completar uma curta-metragem documental.

Title: “Metabolic Reprogramming in the Offspring of Insulin Resistant Parents”
Field: Biology, metabolism
City: Boston, MA
Supervisor: Dario F. de Jesus
Affiliation: Joslin Diabetes Center, Harvard Medical School

The main goals of this internship at the Joslin Diabetes Center (JDC) are 1) to understand the impact of in utero insulin resistance on physiology in the adult offspring 2) to understand paternal-induced metabolic changes in the offspring of insulin resistant fathers.
Diabetes mellitus is a metabolic disease that is mainly characterized by an abnormal raise in plasma glucose concentration. The etiology of the disease is vast and the complications lead to morbidity. Type-1 diabetes (T1D), or insulin- dependent diabetes, is acute, progresses quickly and is characterized by a complete insulin deficiency due to the loss of pancreatic beta cells by various factors (e.g., virus, environmental). Type-2 diabetes (T2D), or non-insulin-dependent diabetes, which was reported to be restricted to adults and elderly individuals, is now also recognized in adolescents due to undetermined factors [1]. Diabetes mellitus is increasing worldwide and by 2030 is expected to affect 366 million people [2]. During 2012 the total estimated cost of diabetes care in USA was 220 billion euros and represented more than 20% of the total health care budget [3]. On the other hand, 12.4% of the Portuguese population lived with diabetes in 2009. This resulted in an estimated total annual cost of 1.3 billion euros, representing 11% of the Portuguese healthcare budget [4]. Despite the identification of more than 100 genes conferring risk of diabetes, only a small portion of the disease risk can be ascribed to the genes. As progression to T2D is largely due to insulin secretory dysfunction and significant beta-cell loss, further research in understanding the epigenetic modifications in offspring beta-cells of insulin resistant parents, will likely play an important role in determining how elevated levels of insulin and glucose itself, influences the expression of important genes in beta cell function and survival.

Title: “CRISPR/Cas9-based Therapeutics for Friedreich’s ataxia”
Field: Molecular biology
City: Boston, MA
Supervisor: Ricardo Mouro Pinto
Affiliation: MGH, Harvard Medical School

O laboratório está inserido no Center for Human Genetic Research (Massachusetts General Hospital / Harvard Medical School) e tem como interesses de investigação os mecanismos genéticos e moleculares causadores de doenças neurodegenerativas como a Ataxia de Friedreich Ataxia (FA) e a doença de Huntington (HD).
FA é uma doença genética rara causada por uma repetição de trinucleótideos GAA que quando expandida resulta num silenciamento genético e consequente redução nos níveis de frataxin.
Em particular, o projeto deste estágio envolve o uso de modelos celulares e técnicas de engenharia genómica com o objetivo de aliviar o silenciamento genético na origem de FA.
O Estagiário vai ser treinado numa série de técnicas laboratoriais de forma a conduzir experiências preliminares que visam desenvolver e validar reagentes capazes de ativar de forma específica a expressão do gene frataxin. Tais técnicas incluem elementos básicos de biologia molecular (extração de DNA, PCR, quantificação de expressão genética, gel eletroforese), cultura de células humanas, transfeções, e CRISPR Cas9.

Title: “Testing clinically relevant matrices for Schwann cell transplantation following spinal cord injury”
Field: Regenerative medicine
City: Miami, FL
Supervisor: Susana Cerqueira
Affiliation: Miller School of Medicine, University of Miami

Cell therapy strategies to repair the injured spinal cord are promising new breakthroughs with the recent clinical trials in acute and chronic spinal cord injury (SCI) subjects [1]. Following an insult to the mammalian spinal cord, a series of complex responses follow that contribute to an aggravated expansion of the initial injury, and result in dramatic functional deficits [2]. The formation of fluid-filled cavities contributes, in part, to the regenerative failure and functional deficits that follow SCI. Cell transplantation strategies rely on reducing cavitation following damage, re-bridging the injured tissue and creating more favorable conditions for axonal regeneration. From the various cell types proposed to be used in SCI repair, Schwann cells (SCs) have been extensively studied and are currently undergoing safety and efficacy evaluation in clinical trials in the Miami Project to Cure Paralysis. SCs are the myelinating glia of the peripheral nervous system, and can be obtained from SCI patients, expanded in culture, and autologously transplanted into the lesioned spinal cord. These cells were found to be neuroprotective, reduce cavitation, promote axon regeneration and myelination, and modestly improve hindlimb movements in animal models [3, 4]. Nevertheless, one of the hurdles that may be limiting the therapeutic potential of SC implants, as well as other cell types, is the poor survival rate of the transplanted cells in the injury site [5]. Previous reports have shown that after a contusion injury in rats, there is about an 80% SC loss 3 weeks after transplantation due to necrosis and apoptosis [6, 7]. The traumatic nature of cell isolation procedures, the detachment from its extracellular matrix (ECM) before transplantation, and the injury environments are some factors that contribute to this significant cell death.
One possible approach to improve transplanted SC survival, therefore maximizing its therapeutic potential, is to implant them in ECM-derived substrates, such as an injectable matrix, instead of the culture media suspension approach. Most commercial ECM matrices, however, are tumor-derived and have undefined and variable growth-factor composition. For these reasons, they are not clinically applicable and it still remains of the utmost importance to identify clinically relevant injectable matrices for achieving greater survival and efficacy of cellular implants after SCI. The goal of this project is to evaluate the potential of ECM-derived matrices in supporting SC survival after injury, while fostering neuronal regeneration through the graft. It will be a project involving concepts and techniques from biomaterials and biomedical research, and envisioning future translational studies for clinical applications.

Title: “Assessment of saturation effects in abundance measurements of extragalactic sight lines using nearby stars”
Field: Astrophysics
City: Baltimore, MD
Supervisor: Cristina Oliveira
Affiliation: Space Telescope Science Institute

Measurements of chemical abundances in local galaxies are different from measurements along single sight lines because light from all the stars in the galaxy is collected as if the galaxy was a single point source. These stars probe different portions of a galaxy, some with different chemical abundances and physical conditions, and can hide saturation effects. Spectra of local galaxies might also have low S/N, which further compounds the problem. This project consists of assessing the saturation effects in abundance measurements of extragalactic sight lines by using nearby stars to measure abundances in each sightline individually as well as in the combined spectrum of all the stars, to simulate a galaxy spectrum. The measurements will use the apparent optical depth technique on echelle data obtained with the Space Telescope Imaging Spectrograph (STIS) onboard the Hubble Space Telescope (HST).

The PAPSummer program will not be offered in 2017. Please check back later this year for updates on the PAPSummer program for 2018 or contact us if you want to be added to the PAPSummer mailing list.